<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/NCT02256969</url>
  </required_header>
  <id_info>
    <org_study_id>14-059H</org_study_id>
    <nct_id>NCT02256969</nct_id>
  </id_info>
  <brief_title>Intraductal Meibomian Gland Probing Trial</brief_title>
  <acronym>MGP</acronym>
  <official_title>Prospective, Randomized Clinical Trial of Meibomian Gland Probing Versus Sham Procedure for Refractory Meibomian Gland Dysfunction</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Joseph B. Ciolino, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Massachusetts Eye and Ear Infirmary</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this research study, the investigators are looking at the effects of Meibomian Gland&#xD;
      Probing (MGP) versus a sham (fake) procedure in patients with refractory MGD who have already&#xD;
      tried traditional management with no success in resolving their clinical signs (as seen by&#xD;
      their ophthalmologist) or their symptoms.&#xD;
&#xD;
      The investigators are also evaluating the effects of using two (2) post-procedural medication&#xD;
      treatments: Blephamide or GenTeal PM Night-Time to determine if treatment after the MGP&#xD;
      procedure has an effect on its outcome.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Dry eye disease is one of the most common conditions seen in ophthalmic practice and is&#xD;
      associated with significant patient distress. Meibomian gland dysfunction (MGD) is among the&#xD;
      most prevalent causes of dry eye disease. This condition, which is often due to obstruction&#xD;
      of the meibomian gland orifices, may result in significant ocular irritation. Traditionally,&#xD;
      management of MGD includes warm compress, lid hygiene, and anti-inflammatory medications.&#xD;
      This randomized clinical trial is designed to evaluate the effects of meibomian gland probing&#xD;
      versus sham procedure in cases with refractory MGD that do not respond to traditional&#xD;
      treatments. Moreover, the effects of postoperative regimen will also be investigated using&#xD;
      two different regimens. In addition to symptoms, the changes will also be evaluated in terms&#xD;
      of clinical signs as well as in vivo confocal microscopy (IVCM) which allows study at the&#xD;
      cellular level.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">August 2015</completion_date>
  <primary_completion_date type="Actual">August 2015</primary_completion_date>
  <phase>Phase 4</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>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Ocular Surface Disease Index (OSDI)</measure>
    <time_frame>4 week Time Point</time_frame>
    <description>A 12-question survey used to measure the symptoms of dry eye disease. Each of the 12 individual questions rate one symptom on a 0-4 scale, with 4 meaning that the symptom is present all of the time and 0 meaning the symptom is present none of the time. The overall ODSI score is calculated by adding all of the values from the 12 questions, multiplying that value by 25, and dividing the resulting value by the number of questions answered. This results in an overall scale that ranges from 0-100, with 100 being severe dry eye symptoms and 0 being no dry eye symptoms.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Symptom Assessment in Dry Eye (SANDE)</measure>
    <time_frame>4 week Time Point</time_frame>
    <description>A two-item survey used to assess the frequency and severity of dry eye disease. The SANDE score is calculated by taking the square root of the product of the frequency of symptoms score and the severity 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 of dry eye symptoms.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Corneal Fluorescein Staining (CFS)</measure>
    <time_frame>4 week Time Point</time_frame>
    <description>Is used to assess the level of corneal epitheliopathy that is related to dry eye disease. The CFS scale ranges from 0 to 15 scale, with 0 representing the minimum level of corneal epitheliopathy and 15 representing the maximum level of epitheliopathy.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Tear Break Up Time (TBUT)</measure>
    <time_frame>4 week Time Point</time_frame>
    <description>TBUT measures the amount of time, in seconds, a dry spot appears in the tear film after each blink. Values less than 10 seconds are considered abnormal.</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">45</enrollment>
  <condition>Meibomian Gland Dysfunction</condition>
  <arm_group>
    <arm_group_label>Meibomian Gland Probing plus lubricant</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Meibomian Gland Probing: Stainless steel probes were used to probe all the meibomian glands of upper lids of both eyes at the slit lamp. All patients were probed with a 1-mm probe followed by a 2-mm probe for all glands.&#xD;
Lubricant: GenTeal PM Night-Time Ointment (Alcon), a sterile ophthalmic lubricant that is commonly used to relieve symptoms in patients with dry eye disease, was applied topically to both eyes for 4 weeks with the following regimen: twice daily for 2 weeks and then once daily for 2 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham Meibomian Gland Probing plus lubricant</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Sham Meibomian Gland Probing: The patient's the lid margin was touched with the probes without actual probing occurring.&#xD;
Lubricant: GenTeal PM Night-Time Ointment, ophthalmic lubricant used to relieve symptoms in patients with dry eye disease, was applied topically to both eyes for 4 weeks: twice daily for 2 weeks and then once daily for 2 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Meibomian Gland Probing plus Blephamide</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Meibomian Gland Probing: Stainless steel probes were used to probe all the meibomian glands of upper lids of both eyes at the slit lamp. All patients were probed with a 1-mm probe followed by a 2-mm probe for all glands.&#xD;
Blephamide: is a combination of an antibiotic and an anti-inflammatory agent commonly used to treat various ocular conditions. Blephamide was applied topically to both eyes for 4 weeks with a regimen of: twice daily for 2 weeks and then once daily for 2 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Blephamide</intervention_name>
    <arm_group_label>Meibomian Gland Probing plus Blephamide</arm_group_label>
    <other_name>sulfacetamide sodium 10%/prednisolone acetate 0.2%, Allergan, Inc.</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GenTeal PM Night-Time</intervention_name>
    <arm_group_label>Meibomian Gland Probing plus lubricant</arm_group_label>
    <arm_group_label>Sham Meibomian Gland Probing plus lubricant</arm_group_label>
    <other_name>GenTeal PM Night-Time Ophthalmic Ointment Alcon</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Meibomian Gland Probing</intervention_name>
    <description>For anesthesia, topical 3.5% lidocaine hydrochloride jelly (Akron) was applied directly with sterile cotton-tipped applicator to the lid margin for 3 times every 10 minutes before the procedure. If necessary, 2% lidocaine was injected into the lid margin during the procedure to provide additional comfort. After obtaining adequate anesthesia, the solid stainless steel probes (Maskin® Meibomian Gland Intraductal Probes, Rhein Medical Inc.) were used to probe all the meibomian glands of upper lids of both eyes at the slit lamp. All patients were initially be probed with a 1-mm probe followed by a 2-mm probe for all glands.</description>
    <arm_group_label>Meibomian Gland Probing plus Blephamide</arm_group_label>
    <arm_group_label>Meibomian Gland Probing plus lubricant</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Sham Meibomian Gland Probing</intervention_name>
    <description>For anesthesia, topical 3.5% lidocaine hydrochloride jelly (Akron) was applied directly with sterile cotton-tipped applicator to the lid margin for 3 times every 10 minutes before the procedure. If necessary, 2% lidocaine was injected into the lid margin during the procedure to provide additional comfort. The patient's lid margin was touched with the probes without actual probing of the meibomian gland orifices.</description>
    <arm_group_label>Sham Meibomian Gland Probing plus lubricant</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18-89 years&#xD;
&#xD;
          -  Willing and able to provide written informed consent&#xD;
&#xD;
          -  Willing and able to comply with study assessments for the full duration of the study&#xD;
&#xD;
          -  Diagnosis of meibomian gland dysfunction (MGD)&#xD;
&#xD;
          -  Symptoms of MGD such as foreign body sensation, burning, stinging, light sensitivity&#xD;
             for at least 3 months&#xD;
&#xD;
          -  Persistent symptoms despite at least 3 months of medical management including lid&#xD;
             hygiene, warm compress, and use of topical and systemic therapy, or contraindication&#xD;
             to systemic therapy&#xD;
&#xD;
          -  Presence of lid tenderness on the upper lids in both eyes&#xD;
&#xD;
          -  Tear break-up time (TBUT) of &lt;10 seconds&#xD;
&#xD;
          -  In good stable overall health&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active allergies to steroids, sulfacetamide, GenTeal PM Night-Time ointment, or&#xD;
             lidocaine&#xD;
&#xD;
          -  Intraocular surgery or ocular laser surgery within 1 month before enrollment&#xD;
&#xD;
          -  History of ocular infection within 1 month before enrollment.&#xD;
&#xD;
          -  History of increased intraocular pressure after using topical steroids (steroid&#xD;
             responsive)&#xD;
&#xD;
          -  Any condition (including language barrier) that precludes subject's ability to comply&#xD;
             with study requirements including completion of study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>89 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joseph B Ciolino, M. D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts Eye and Ear Infirmary</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Massachusetts Eye and Ear Infirmary</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>August 13, 2014</study_first_submitted>
  <study_first_submitted_qc>October 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 6, 2014</study_first_posted>
  <results_first_submitted>April 14, 2017</results_first_submitted>
  <results_first_submitted_qc>April 14, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">May 22, 2017</results_first_posted>
  <last_update_submitted>May 25, 2017</last_update_submitted>
  <last_update_submitted_qc>May 25, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">June 19, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts Eye and Ear Infirmary</investigator_affiliation>
    <investigator_full_name>Joseph B. Ciolino, MD</investigator_full_name>
    <investigator_title>Assistant Professor of Ophthalmology</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Meibomian Gland Dysfunction</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sulfacetamide</mesh_term>
    <mesh_term>Prednisolone</mesh_term>
    <mesh_term>Methylprednisolone Acetate</mesh_term>
    <mesh_term>Methylprednisolone</mesh_term>
    <mesh_term>Methylprednisolone Hemisuccinate</mesh_term>
    <mesh_term>Prednisolone acetate</mesh_term>
    <mesh_term>Mineral Oil</mesh_term>
    <mesh_term>Prednisolone hemisuccinate</mesh_term>
    <mesh_term>Prednisolone phosphate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Meibomian Gland Probing Plus Lubricant</title>
          <description>Meibomian Gland Probing: Stainless steel probes were used to probe all the meibomian glands of upper lids of both eyes at the slit lamp.&#xD;
Lubricant: GenTeal PM Night-Time Ointment, an ophthalmic lubricant that is used to relieve symptoms in patients with dry eye disease; was applied topically to both eyes for 4 weeks: twice daily for 2 weeks and then once daily for 2 weeks.</description>
        </group>
        <group group_id="P2">
          <title>Sham Meibomian Gland Probing Plus Lubricant</title>
          <description>Sham Meibomian Gland Probing: The patient's the lid margin was touched with the probes without actual probing occurring.&#xD;
Lubricant: GenTeal PM Night-Time Ointment, ophthalmic lubricant used to relieve symptoms in patients with dry eye disease, was applied topically to both eyes for 4 weeks: twice daily for 2 weeks and then once daily for 2 weeks.</description>
        </group>
        <group group_id="P3">
          <title>Meibomian Gland Probing Plus Blephamide</title>
          <description>Meibomian Gland Probing: Stainless steel probes were used to probe the meibomian glands of upper lids of both eyes. All patients were probed with a 1-mm probe followed by a 2-mm probe for all glands.&#xD;
Blephamide: is a combination of an antibiotic and an anti-inflammatory agent commonly used to treat various ocular conditions. Blephamide was applied topically to both eyes for 4 weeks with a regimen of: twice daily for 2 weeks and then once daily for 2 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="15"/>
                <participants group_id="P3" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="14"/>
                <participants group_id="P3" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Screenfailed or withdrew</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Meibomian Gland Probing Plus Lubricant</title>
          <description>Meibomian Gland Probing: Stainless steel probes were used to probe all the meibomian glands of upper lids of both eyes at the slit lamp.&#xD;
Lubricant: GenTeal PM Night-Time Ointment, an ophthalmic lubricant that is used to relieve symptoms in patients with dry eye disease; was applied topically to both eyes for 4 weeks: twice daily for 2 weeks and then once daily for 2 weeks.</description>
        </group>
        <group group_id="B2">
          <title>Sham Meibomian Gland Probing Plus Lubricant</title>
          <description>Sham Meibomian Gland Probing: The patient's the lid margin was touched with the probes without actual probing occurring.&#xD;
Lubricant: GenTeal PM Night-Time Ointment, ophthalmic lubricant used to relieve symptoms in patients with dry eye disease, was applied topically to both eyes for 4 weeks: twice daily for 2 weeks and then once daily for 2 weeks.</description>
        </group>
        <group group_id="B3">
          <title>Meibomian Gland Probing Plus Blephamide</title>
          <description>Meibomian Gland Probing: Stainless steel probes were used to probe the meibomian glands of upper lids of both eyes. All patients were probed with a 1-mm probe followed by a 2-mm probe for all glands.&#xD;
Blephamide: is a combination of an antibiotic and an anti-inflammatory agent commonly used to treat various ocular conditions. Blephamide was applied topically to both eyes for 4 weeks with a regimen of: twice daily for 2 weeks and then once daily for 2 weeks.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="13"/>
            <count group_id="B2" value="14"/>
            <count group_id="B3" value="14"/>
            <count group_id="B4" value="41"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59.6" spread="13.7"/>
                    <measurement group_id="B2" value="63.9" spread="13.8"/>
                    <measurement group_id="B3" value="59.8" spread="17.4"/>
                    <measurement group_id="B4" value="61.1" spread="15.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ocular Surface Disease Index (OSDI)</title>
          <description>The overall ODSI score is calculated by adding all of the values from the 12 questions, multiplying that value by 25, and dividing the resulting value by the number of questions answered. This results in an overall scale that ranges from 0-100, with 100 being severe dry eye symptoms and 0 being no dry eye symptoms.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="45.3" spread="23.8"/>
                    <measurement group_id="B2" value="49.1" spread="27.1"/>
                    <measurement group_id="B3" value="49.1" spread="19.9"/>
                    <measurement group_id="B4" value="47.9" spread="23.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Symptom Assessment in Dry Eye (SANDE)</title>
          <description>A two-item survey used to assess the frequency and severity of dry eye disease. The SANDE score is calculated by taking the square root of the product of the frequency of symptoms score and the severity 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 of dry eye symptoms.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="68.7" spread="15.4"/>
                    <measurement group_id="B2" value="61.8" spread="22.5"/>
                    <measurement group_id="B3" value="72.1" spread="14.1"/>
                    <measurement group_id="B4" value="67.5" spread="17.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Corneal Fluorescein Staining (CFS)</title>
          <description>The Corneal Fluorescein Staining (CFS) scale ranges from 0 to 15 scale, with 0 representing the minimum level of corneal epitheliopathy and 15 representing the maximum level of epitheliopathy.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1.9" spread="1.6"/>
                    <measurement group_id="B2" value="2.0" spread="2.0"/>
                    <measurement group_id="B3" value="0.9" spread="1.0"/>
                    <measurement group_id="B4" value="1.6" spread="1.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Tear Film Break-Up Time (TBUT)</title>
          <description>TBUT measures the amount of time, in seconds, a dry spot appears in the tear film after each blink. Values less than 10 seconds are considered abnormal.</description>
          <units>Seconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2.9" spread="1.5"/>
                    <measurement group_id="B2" value="3.0" spread="1.5"/>
                    <measurement group_id="B3" value="2.3" spread="2.5"/>
                    <measurement group_id="B4" value="3.0" spread="1.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Ocular Surface Disease Index (OSDI)</title>
        <description>A 12-question survey used to measure the symptoms of dry eye disease. Each of the 12 individual questions rate one symptom on a 0-4 scale, with 4 meaning that the symptom is present all of the time and 0 meaning the symptom is present none of the time. The overall ODSI score is calculated by adding all of the values from the 12 questions, multiplying that value by 25, and dividing the resulting value by the number of questions answered. This results in an overall scale that ranges from 0-100, with 100 being severe dry eye symptoms and 0 being no dry eye symptoms.</description>
        <time_frame>4 week Time Point</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Meibomian Gland Probing Plus Lubricant</title>
            <description>Meibomian Gland Probing: Stainless steel probes were used to probe all the meibomian glands of upper lids of both eyes at the slit lamp.&#xD;
Lubricant: GenTeal PM Night-Time Ointment, an ophthalmic lubricant that is used to relieve symptoms in patients with dry eye disease; was applied topically to both eyes for 4 weeks: twice daily for 2 weeks and then once daily for 2 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sham Meibomian Gland Probing Plus Lubricant</title>
            <description>Sham Meibomian Gland Probing: The patient's the lid margin was touched with the probes without actual probing occurring.&#xD;
Lubricant: GenTeal PM Night-Time Ointment, ophthalmic lubricant used to relieve symptoms in patients with dry eye disease, was applied topically to both eyes for 4 weeks: twice daily for 2 weeks and then once daily for 2 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Meibomian Gland Probing Plus Blephamide</title>
            <description>Meibomian Gland Probing: Stainless steel probes were used to probe the meibomian glands of upper lids of both eyes. All patients were probed with a 1-mm probe followed by a 2-mm probe for all glands.&#xD;
Blephamide: is a combination of an antibiotic and an anti-inflammatory agent commonly used to treat various ocular conditions. Blephamide was applied topically to both eyes for 4 weeks with a regimen of: twice daily for 2 weeks and then once daily for 2 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Ocular Surface Disease Index (OSDI)</title>
          <description>A 12-question survey used to measure the symptoms of dry eye disease. Each of the 12 individual questions rate one symptom on a 0-4 scale, with 4 meaning that the symptom is present all of the time and 0 meaning the symptom is present none of the time. The overall ODSI score is calculated by adding all of the values from the 12 questions, multiplying that value by 25, and dividing the resulting value by the number of questions answered. This results in an overall scale that ranges from 0-100, with 100 being severe dry eye symptoms and 0 being no dry eye symptoms.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="14"/>
                <count group_id="O3" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38.7" spread="20.3"/>
                    <measurement group_id="O2" value="36.9" spread="28.2"/>
                    <measurement group_id="O3" value="37.3" spread="21.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Symptom Assessment in Dry Eye (SANDE)</title>
        <description>A two-item survey used to assess the frequency and severity of dry eye disease. The SANDE score is calculated by taking the square root of the product of the frequency of symptoms score and the severity 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 of dry eye symptoms.</description>
        <time_frame>4 week Time Point</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Meibomian Gland Probing Plus Lubricant</title>
            <description>Meibomian Gland Probing: Stainless steel probes were used to probe all the meibomian glands of upper lids of both eyes at the slit lamp.&#xD;
Lubricant: GenTeal PM Night-Time Ointment, an ophthalmic lubricant that is used to relieve symptoms in patients with dry eye disease; was applied topically to both eyes for 4 weeks: twice daily for 2 weeks and then once daily for 2 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sham Meibomian Gland Probing Plus Lubricant</title>
            <description>Sham Meibomian Gland Probing: The patient's the lid margin was touched with the probes without actual probing occurring.&#xD;
Lubricant: GenTeal PM Night-Time Ointment, ophthalmic lubricant used to relieve symptoms in patients with dry eye disease, was applied topically to both eyes for 4 weeks: twice daily for 2 weeks and then once daily for 2 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Meibomian Gland Probing Plus Blephamide</title>
            <description>Meibomian Gland Probing: Stainless steel probes were used to probe the meibomian glands of upper lids of both eyes. All patients were probed with a 1-mm probe followed by a 2-mm probe for all glands.&#xD;
Blephamide: is a combination of an antibiotic and an anti-inflammatory agent commonly used to treat various ocular conditions. Blephamide was applied topically to both eyes for 4 weeks with a regimen of: twice daily for 2 weeks and then once daily for 2 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Symptom Assessment in Dry Eye (SANDE)</title>
          <description>A two-item survey used to assess the frequency and severity of dry eye disease. The SANDE score is calculated by taking the square root of the product of the frequency of symptoms score and the severity 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 of dry eye symptoms.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="14"/>
                <count group_id="O3" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49.1" spread="22.5"/>
                    <measurement group_id="O2" value="50.2" spread="27.6"/>
                    <measurement group_id="O3" value="47.6" spread="25.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Corneal Fluorescein Staining (CFS)</title>
        <description>Is used to assess the level of corneal epitheliopathy that is related to dry eye disease. The CFS scale ranges from 0 to 15 scale, with 0 representing the minimum level of corneal epitheliopathy and 15 representing the maximum level of epitheliopathy.</description>
        <time_frame>4 week Time Point</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Meibomian Gland Probing Plus Lubricant</title>
            <description>Meibomian Gland Probing: Stainless steel probes were used to probe all the meibomian glands of upper lids of both eyes at the slit lamp.&#xD;
Lubricant: GenTeal PM Night-Time Ointment, an ophthalmic lubricant that is used to relieve symptoms in patients with dry eye disease; was applied topically to both eyes for 4 weeks: twice daily for 2 weeks and then once daily for 2 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sham Meibomian Gland Probing Plus Lubricant</title>
            <description>Sham Meibomian Gland Probing: The patient's the lid margin was touched with the probes without actual probing occurring.&#xD;
Lubricant: GenTeal PM Night-Time Ointment, ophthalmic lubricant used to relieve symptoms in patients with dry eye disease, was applied topically to both eyes for 4 weeks: twice daily for 2 weeks and then once daily for 2 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Meibomian Gland Probing Plus Blephamide</title>
            <description>Meibomian Gland Probing: Stainless steel probes were used to probe the meibomian glands of upper lids of both eyes. All patients were probed with a 1-mm probe followed by a 2-mm probe for all glands.&#xD;
Blephamide: is a combination of an antibiotic and an anti-inflammatory agent commonly used to treat various ocular conditions. Blephamide was applied topically to both eyes for 4 weeks with a regimen of: twice daily for 2 weeks and then once daily for 2 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Corneal Fluorescein Staining (CFS)</title>
          <description>Is used to assess the level of corneal epitheliopathy that is related to dry eye disease. The CFS scale ranges from 0 to 15 scale, with 0 representing the minimum level of corneal epitheliopathy and 15 representing the maximum level of epitheliopathy.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="14"/>
                <count group_id="O3" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.4" spread="2.4"/>
                    <measurement group_id="O2" value="2.0" spread="2.2"/>
                    <measurement group_id="O3" value="1.4" spread="2.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Tear Break Up Time (TBUT)</title>
        <description>TBUT measures the amount of time, in seconds, a dry spot appears in the tear film after each blink. Values less than 10 seconds are considered abnormal.</description>
        <time_frame>4 week Time Point</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Meibomian Gland Probing Plus Lubricant</title>
            <description>Meibomian Gland Probing: Stainless steel probes were used to probe all the meibomian glands of upper lids of both eyes at the slit lamp.&#xD;
Lubricant: GenTeal PM Night-Time Ointment, an ophthalmic lubricant that is used to relieve symptoms in patients with dry eye disease; was applied topically to both eyes for 4 weeks: twice daily for 2 weeks and then once daily for 2 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Sham Meibomian Gland Probing Plus Lubricant</title>
            <description>Sham Meibomian Gland Probing: The patient's the lid margin was touched with the probes without actual probing occurring.&#xD;
Lubricant: GenTeal PM Night-Time Ointment, ophthalmic lubricant used to relieve symptoms in patients with dry eye disease, was applied topically to both eyes for 4 weeks: twice daily for 2 weeks and then once daily for 2 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Meibomian Gland Probing Plus Blephamide</title>
            <description>Meibomian Gland Probing: Stainless steel probes were used to probe the meibomian glands of upper lids of both eyes. All patients were probed with a 1-mm probe followed by a 2-mm probe for all glands.&#xD;
Blephamide: is a combination of an antibiotic and an anti-inflammatory agent commonly used to treat various ocular conditions. Blephamide was applied topically to both eyes for 4 weeks with a regimen of: twice daily for 2 weeks and then once daily for 2 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Tear Break Up Time (TBUT)</title>
          <description>TBUT measures the amount of time, in seconds, a dry spot appears in the tear film after each blink. Values less than 10 seconds are considered abnormal.</description>
          <units>Seconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="14"/>
                <count group_id="O3" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.5" spread="2.4"/>
                    <measurement group_id="O2" value="4.2" spread="3.0"/>
                    <measurement group_id="O3" value="3.2" spread="2.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>4 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Meibomian Gland Probing Plus Lubricant</title>
          <description>Meibomian Gland Probing: Stainless steel probes were used to probe all the meibomian glands of upper lids of both eyes at the slit lamp.&#xD;
Lubricant: GenTeal PM Night-Time Ointment, an ophthalmic lubricant that is used to relieve symptoms in patients with dry eye disease; was applied topically to both eyes for 4 weeks: twice daily for 2 weeks and then once daily for 2 weeks.</description>
        </group>
        <group group_id="E2">
          <title>Sham Meibomian Gland Probing Plus Lubricant</title>
          <description>Sham Meibomian Gland Probing: The patient's the lid margin was touched with the probes without actual probing occurring.&#xD;
Lubricant: GenTeal PM Night-Time Ointment, ophthalmic lubricant used to relieve symptoms in patients with dry eye disease, was applied topically to both eyes for 4 weeks: twice daily for 2 weeks and then once daily for 2 weeks.</description>
        </group>
        <group group_id="E3">
          <title>Meibomian Gland Probing Plus Blephamide</title>
          <description>Meibomian Gland Probing: Stainless steel probes were used to probe the meibomian glands of upper lids of both eyes. All patients were probed with a 1-mm probe followed by a 2-mm probe for all glands.&#xD;
Blephamide: is a combination of an antibiotic and an anti-inflammatory agent commonly used to treat various ocular conditions. Blephamide was applied topically to both eyes for 4 weeks with a regimen of: twice daily for 2 weeks and then once daily for 2 weeks.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Eye Pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Redness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Foreign Body Sensation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Assistant Professor of Ophthalmology</name_or_title>
      <organization>Massachusetts Eye and Ear Infirmary</organization>
      <phone>617-573-6060 ext 6060</phone>
      <email>ophthalmologyclinicalresearch@meei.harvard.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02256969
org study id: 14-059H
nct id: NCT02256969
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
In this research study, the investigators are looking at the effects of Meibomian Gland
      Probing (MGP) versus a sham (fake) procedure in patients with refractory MGD who have already
      tried traditional management with no success in resolving their clinical signs (as seen by
      their ophthalmologist) or their symptoms.

      The investigators are also evaluating the effects of using two (2) post-procedural medication
      treatments: Blephamide or GenTeal PM Night-Time to determine if treatment after the MGP
      procedure has an effect on its outcome.
Dry eye disease is one of the most common conditions seen in ophthalmic practice and is
      associated with significant patient distress. Meibomian gland dysfunction (MGD) is among the
      most prevalent causes of dry eye disease. This condition, which is often due to obstruction
      of the meibomian gland orifices, may result in significant ocular irritation. Traditionally,
      management of MGD includes warm compress, lid hygiene, and anti-inflammatory medications.
      This randomized clinical trial is designed to evaluate the effects of meibomian gland probing
      versus sham procedure in cases with refractory MGD that do not respond to traditional
      treatments. Moreover, the effects of postoperative regimen will also be investigated using
      two different regimens. In addition to symptoms, the changes will also be evaluated in terms
      of clinical signs as well as in vivo confocal microscopy (IVCM) which allows study at the
      cellular level.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Ocular Surface Disease Index (OSDI)
time frame: 4 week Time Point
description: A 12-question survey used to measure the symptoms of dry eye disease. Each of the 12 individual questions rate one symptom on a 0-4 scale, with 4 meaning that the symptom is present all of the time and 0 meaning the symptom is present none of the time. The overall ODSI score is calculated by adding all of the values from the 12 questions, multiplying that value by 25, and dividing the resulting value by the number of questions answered. This results in an overall scale that ranges from 0-100, with 100 being severe dry eye symptoms and 0 being no dry eye symptoms.
measure: Symptom Assessment in Dry Eye (SANDE)
time frame: 4 week Time Point
description: A two-item survey used to assess the frequency and severity of dry eye disease. The SANDE score is calculated by taking the square root of the product of the frequency of symptoms score and the severity 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 of dry eye symptoms.
measure: Corneal Fluorescein Staining (CFS)
time frame: 4 week Time Point
description: Is used to assess the level of corneal epitheliopathy that is related to dry eye disease. The CFS scale ranges from 0 to 15 scale, with 0 representing the minimum level of corneal epitheliopathy and 15 representing the maximum level of epitheliopathy.
measure: Tear Break Up Time (TBUT)
time frame: 4 week Time Point
description: TBUT measures the amount of time, in seconds, a dry spot appears in the tear film after each blink. Values less than 10 seconds are considered abnormal.
arm group label: Meibomian Gland Probing plus lubricant
arm group type: Other
description: Meibomian Gland Probing: Stainless steel probes were used to probe all the meibomian glands of upper lids of both eyes at the slit lamp. All patients were probed with a 1-mm probe followed by a 2-mm probe for all glands.
Lubricant: GenTeal PM Night-Time Ointment (Alcon), a sterile ophthalmic lubricant that is commonly used to relieve symptoms in patients with dry eye disease, was applied topically to both eyes for 4 weeks with the following regimen: twice daily for 2 weeks and then once daily for 2 weeks.
arm group label: Sham Meibomian Gland Probing plus lubricant
arm group type: Other
description: Sham Meibomian Gland Probing: The patient's the lid margin was touched with the probes without actual probing occurring.
Lubricant: GenTeal PM Night-Time Ointment, ophthalmic lubricant used to relieve symptoms in patients with dry eye disease, was applied topically to both eyes for 4 weeks: twice daily for 2 weeks and then once daily for 2 weeks.
arm group label: Meibomian Gland Probing plus Blephamide
arm group type: Active Comparator
description: Meibomian Gland Probing: Stainless steel probes were used to probe all the meibomian glands of upper lids of both eyes at the slit lamp. All patients were probed with a 1-mm probe followed by a 2-mm probe for all glands.
Blephamide: is a combination of an antibiotic and an anti-inflammatory agent commonly used to treat various ocular conditions. Blephamide was applied topically to both eyes for 4 weeks with a regimen of: twice daily for 2 weeks and then once daily for 2 weeks.
intervention type: Drug
intervention name: Blephamide
arm group label: Meibomian Gland Probing plus Blephamide
other name: sulfacetamide sodium 10%/prednisolone acetate 0.2%, Allergan, Inc.
intervention type: Drug
intervention name: GenTeal PM Night-Time
arm group label: Meibomian Gland Probing plus lubricant
arm group label: Sham Meibomian Gland Probing plus lubricant
other name: GenTeal PM Night-Time Ophthalmic Ointment Alcon
intervention type: Procedure
intervention name: Meibomian Gland Probing
description: For anesthesia, topical 3.5% lidocaine hydrochloride jelly (Akron) was applied directly with sterile cotton-tipped applicator to the lid margin for 3 times every 10 minutes before the procedure. If necessary, 2% lidocaine was injected into the lid margin during the procedure to provide additional comfort. After obtaining adequate anesthesia, the solid stainless steel probes (Maskin® Meibomian Gland Intraductal Probes, Rhein Medical Inc.) were used to probe all the meibomian glands of upper lids of both eyes at the slit lamp. All patients were initially be probed with a 1-mm probe followed by a 2-mm probe for all glands.
arm group label: Meibomian Gland Probing plus Blephamide
arm group label: Meibomian Gland Probing plus lubricant
intervention type: Procedure
intervention name: Sham Meibomian Gland Probing
description: For anesthesia, topical 3.5% lidocaine hydrochloride jelly (Akron) was applied directly with sterile cotton-tipped applicator to the lid margin for 3 times every 10 minutes before the procedure. If necessary, 2% lidocaine was injected into the lid margin during the procedure to provide additional comfort. The patient's lid margin was touched with the probes without actual probing of the meibomian gland orifices.
arm group label: Sham Meibomian Gland Probing plus lubricant
criteria: 
gender: All
minimum age: 18 Years
maximum age: 89 Years
healthy volunteers: No
last name: Joseph B Ciolino, M. D.
role: Principal Investigator
affiliation: Massachusetts Eye and Ear Infirmary
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Massachusetts Eye and Ear Infirmary
investigator full name: Joseph B. Ciolino, MD
investigator title: Assistant Professor of Ophthalmology
mesh term: Meibomian Gland Dysfunction
mesh term: Sulfacetamide
mesh term: Prednisolone
mesh term: Methylprednisolone Acetate
mesh term: Methylprednisolone
mesh term: Methylprednisolone Hemisuccinate
mesh term: Prednisolone acetate
mesh term: Mineral Oil
mesh term: Prednisolone hemisuccinate
mesh term: Prednisolone phosphate
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 