<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/NCT04423341</url>
  </required_header>
  <id_info>
    <org_study_id>1268646</org_study_id>
    <nct_id>NCT04423341</nct_id>
  </id_info>
  <brief_title>Effect of Non-psychoactive Cannabidiol as an Adjunct to Botulinum Toxin in Blepharospasm</brief_title>
  <official_title>Effect of Non-psychoactive Cannabidiol as an Adjunct to Botulinum Toxin in Blepharospasm - a Prospective Double-masked Cross-over Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Silkiss Eye Surgery</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Benign Essential Blepharospasm Research Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Jazz Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Smith-Kettlewell Eye Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Silkiss Eye Surgery</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The planned study is a prospective analysis of non-psychoactive Cannabidiol (without THC) as&#xD;
      an adjunctive therapy for blepharospasm in a masked double cross-over study. This prospective&#xD;
      study is a follow-up to a retrospective study completed by the researchers using&#xD;
      over-the-counter, self purchased CBD. This study will use FDA approved Cannabidiol&#xD;
      medication, Epidiolex, directly from GW pharmaceuticals, rather than self-purchased CBD from&#xD;
      the internet. Patients will undergo videorecording with a high resolution videocamera system&#xD;
      at days 0, 45, 90, 135, and 180 using a novel blink analysis to gather objective data&#xD;
      measurements of changes induced by CBD in Blepharospasm patients. This study will attempt to&#xD;
      codify the data and quantify if adjunctive CBD therapy improves those areas compared to&#xD;
      botulinum injection alone.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 20, 2020</start_date>
  <completion_date type="Actual">October 1, 2021</completion_date>
  <primary_completion_date type="Actual">March 22, 2021</primary_completion_date>
  <phase>Phase 2/Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Eyeblink analysis from high speed videocamera recordings - see separate outcome measures</measure>
    <time_frame>4 measurements over 6 months</time_frame>
    <description>All patients will undergo video recording of their eyelid kinematics at days 0, 45, 90, 135, and 180. A high-resolution commercially available video camera will capture the eyelid positions at a sampling rate of thirty frames per second. Patients will be assessed in three different lighting conditions - in regular exam room lighting, under examination with the glare source of an indirect ophthalmoscope (at 2000 lux on both eyes from 5 feet), and in dim lighting. The upper and lower eyelid positions captured from each frame of the videos will be input into custom software developed by Visage Technologies, which fits a feature template to the facial features in each frame, including the upper and lower lids of each eye. The difference between the upper and lower lid positions defined the lid aperture, also known as the palpebral fissure. The eyeblink parameters will then calculated from the eyelid aperture time series with custom software written in MATLAB.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Median Blink Amplitude</measure>
    <time_frame>4 measurements over 6 months</time_frame>
    <description>Measured in millimeters (mm)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Median Blink Duration</measure>
    <time_frame>4 measurements over 6 months</time_frame>
    <description>Measured in milliseconds (ms)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Max Blink Velocity</measure>
    <time_frame>4 measurements over 6 months</time_frame>
    <description>Measured in millimeters per milliseconds (mm/ms)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Blinks per 100ms</measure>
    <time_frame>4 measurements over 6 months</time_frame>
    <description>Total &quot;blinks&quot; in 100 milliseconds (numeric value)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Blepharospasm</condition>
  <condition>Blepharospasm, Benign Essential</condition>
  <condition>CBD</condition>
  <arm_group>
    <arm_group_label>Group A - active medication followed by placebo</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B - placebo followed by active medication</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cannabidiol Oral Solution [Epidiolex]</intervention_name>
    <description>100 mg BID for three months Placebo oral solution for three months</description>
    <arm_group_label>Group A - active medication followed by placebo</arm_group_label>
    <arm_group_label>Group B - placebo followed by active medication</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients in the private practice of the principal investigator with an ICD code of&#xD;
             &quot;blepharospasm&quot; and:&#xD;
&#xD;
          -  undergoing routine maximal botulinum therapy&#xD;
&#xD;
          -  experiencing break through symptoms of spasm&#xD;
&#xD;
          -  marijuana naïve&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  concomitant diagnosis of epilepsy&#xD;
&#xD;
          -  patients whom are not marijuana naive&#xD;
&#xD;
          -  patients on concurrent anti-epileptics&#xD;
&#xD;
          -  patients who are pregnant or wishing to become pregnant&#xD;
&#xD;
          -  patients not wishing to participate in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Silkiss Eye Surgery</name>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <zip>94609</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>May 28, 2020</study_first_submitted>
  <study_first_submitted_qc>June 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>October 29, 2021</last_update_submitted>
  <last_update_submitted_qc>October 29, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 2, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Silkiss Eye Surgery</investigator_affiliation>
    <investigator_full_name>Rona Silkiss, MD FACS</investigator_full_name>
    <investigator_title>Physician</investigator_title>
  </responsible_party>
  <keyword>Cannabidiol</keyword>
  <keyword>Epidiolex</keyword>
  <keyword>Botulinum Toxin</keyword>
  <keyword>Eyeblink analysis</keyword>
  <keyword>Videorecording</keyword>
  <keyword>Blepharospasm</keyword>
  <keyword>BEB</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Blepharospasm</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cannabidiol</mesh_term>
  </intervention_browse>
  <!-- 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/NCT04423341
org study id: 1268646
nct id: NCT04423341
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The planned study is a prospective analysis of non-psychoactive Cannabidiol (without THC) as
      an adjunctive therapy for blepharospasm in a masked double cross-over study. This prospective
      study is a follow-up to a retrospective study completed by the researchers using
      over-the-counter, self purchased CBD. This study will use FDA approved Cannabidiol
      medication, Epidiolex, directly from GW pharmaceuticals, rather than self-purchased CBD from
      the internet. Patients will undergo videorecording with a high resolution videocamera system
      at days 0, 45, 90, 135, and 180 using a novel blink analysis to gather objective data
      measurements of changes induced by CBD in Blepharospasm patients. This study will attempt to
      codify the data and quantify if adjunctive CBD therapy improves those areas compared to
      botulinum injection alone.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Eyeblink analysis from high speed videocamera recordings - see separate outcome measures
time frame: 4 measurements over 6 months
description: All patients will undergo video recording of their eyelid kinematics at days 0, 45, 90, 135, and 180. A high-resolution commercially available video camera will capture the eyelid positions at a sampling rate of thirty frames per second. Patients will be assessed in three different lighting conditions - in regular exam room lighting, under examination with the glare source of an indirect ophthalmoscope (at 2000 lux on both eyes from 5 feet), and in dim lighting. The upper and lower eyelid positions captured from each frame of the videos will be input into custom software developed by Visage Technologies, which fits a feature template to the facial features in each frame, including the upper and lower lids of each eye. The difference between the upper and lower lid positions defined the lid aperture, also known as the palpebral fissure. The eyeblink parameters will then calculated from the eyelid aperture time series with custom software written in MATLAB.
measure: Median Blink Amplitude
time frame: 4 measurements over 6 months
description: Measured in millimeters (mm)
measure: Median Blink Duration
time frame: 4 measurements over 6 months
description: Measured in milliseconds (ms)
measure: Median Max Blink Velocity
time frame: 4 measurements over 6 months
description: Measured in millimeters per milliseconds (mm/ms)
measure: Number of Blinks per 100ms
time frame: 4 measurements over 6 months
description: Total "blinks" in 100 milliseconds (numeric value)
arm group label: Group A - active medication followed by placebo
arm group type: Active Comparator
arm group label: Group B - placebo followed by active medication
arm group type: Active Comparator
intervention type: Drug
intervention name: Cannabidiol Oral Solution [Epidiolex]
description: 100 mg BID for three months Placebo oral solution for three months
arm group label: Group A - active medication followed by placebo
arm group label: Group B - placebo followed by active medication
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Silkiss Eye Surgery
investigator full name: Rona Silkiss, MD FACS
investigator title: Physician
mesh term: Blepharospasm
mesh term: Cannabidiol