<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/NCT03263000</url>
  </required_header>
  <id_info>
    <org_study_id>170159</org_study_id>
    <secondary_id>17-N-0159</secondary_id>
    <nct_id>NCT03263000</nct_id>
  </id_info>
  <brief_title>Photic Blink Reflex in People With Blepharospasm and Increased Blinking</brief_title>
  <official_title>Study of the Photic Blink Reflex in Patients With Blepharospasm and Increased Blinking</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Neurological Disorders and Stroke (NINDS)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institutes of Health Clinical Center (CC)</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      Some people who have increased blinking may later develop blepharospasm. Blepharospasm is a&#xD;
      neurological disorder that causes involuntary closing of the eyes. Researchers want to learn&#xD;
      more about how eyes close in response to different stimuli. They want to study this in&#xD;
      healthy people, people with increased blinking, and people with blepharospasm.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To learn how light exposure affects people with blepharospasm.&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      People ages 18 and older with blepharospasm or increased blinking, and healthy volunteers&#xD;
&#xD;
      Design:&#xD;
&#xD;
      Participants will be screened with:&#xD;
&#xD;
      Medical history&#xD;
&#xD;
      Physical exam&#xD;
&#xD;
      Neurological exam&#xD;
&#xD;
      Participants will have up to 5 visits. The number of visits will depend on the number of&#xD;
      tests they opt to have. They can opt to have up to 4 tests. Visits last 60-90 minutes. They&#xD;
      cannot drink alcohol or caffeinated drinks for at least 12 hours before visits. Visits could&#xD;
      include the following tests:&#xD;
&#xD;
      Evaluation of eyelid movements. This will be video recorded.&#xD;
&#xD;
      Electromyography: Small sticky electrodes are placed on the lower eyelid skin. These are&#xD;
      attached to wires. Muscle activity is recorded during blink reflex procedures.&#xD;
&#xD;
      Electrical stimulation: An electrode is placed close to the eyebrow. It will deliver small&#xD;
      electrical shocks. The strength of the shocks will be enough to provoke a blink.&#xD;
&#xD;
      Photic stimulation: A lamp is placed in front of the face. It will deliver single or paired&#xD;
      flashes. The flashes will be at various intervals and intensities. Participants will wear a&#xD;
      patch over one eye during this test.&#xD;
&#xD;
      Combination of electrical and photic stimulation&#xD;
&#xD;
      ...&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Objective:&#xD;
&#xD;
        -  The purpose of the first study of this protocol is to improve understanding of the role&#xD;
           played by light sensitivity in the pathophysiology of blepharospasm (BPS).&#xD;
&#xD;
        -  As a characteristic feature of BPS, the electrocutaneous blink reflex recovery cycle&#xD;
           (EBR rc) shows an increased recovery index of R2 compared with healthy subjects.&#xD;
&#xD;
        -  In the first study proposed under this protocol we will study the recovery cycle of the&#xD;
           blink reflex evoked by a light stimulus (PBR rc) and the effect of a light stimulus on&#xD;
           the EBR (MBR rc) in patient with BPS. Since photophobia and increased blinking are&#xD;
           common symptoms in this group of patients, we will look for possible correlations&#xD;
           between neurophysiological data and the Light Sensitivity Questionnaire (LSQ) or the&#xD;
           Blink rate (Brt). The second study proposed under this protocol will explore the PBR rc&#xD;
           and the MBR rc in patients with increased blinking alone, a condition indicated as a&#xD;
           possible precursor of BPS.&#xD;
&#xD;
      Study population:&#xD;
&#xD;
      We plan to recruit 24 patients with blepharospasm, 24 healthy volunteers (HVs) and 24&#xD;
      patients with increased blinking alone.&#xD;
&#xD;
      Design:&#xD;
&#xD;
      In two different studies, we will compare all the results from the EBR rc, PBR rc and MBR rc&#xD;
      between BPS patients (first study) or increased blinking patients (second study) and HVs. We&#xD;
      will also look for possible correlation between the neurophysiologic data and the clinical&#xD;
      scales acquired during a clinical assessment. In the EBR rc procedure, the supraorbital nerve&#xD;
      will be stimulated with paired electrical stimuli at varying ISIs and the EMG response from&#xD;
      the orbicularis oculi muscles will be recorded. In the PBR rc procedure, paired light stimuli&#xD;
      will be given at varying interstimulus intervals (ISIs) and the EMG responses from the&#xD;
      orbicularis oculi will be recorded. In the MBR rc study a weak light stimulation will be&#xD;
      given at varying ISIs before an electrical stimulation of the supraorbital nerve. Each&#xD;
      experimental procedure will last about 1 hour. There will be one screening visit and up to 4&#xD;
      testing visits per participant. However, participant can either undergo all the experimental&#xD;
      procedures or participate in only some of them and will be allowed to participate in two&#xD;
      experimental procedures per testing visit.&#xD;
&#xD;
      Outcome measurements:&#xD;
&#xD;
        -  EBR rc, PBR rc, MBR rc: the electromyography (EMG) responses at different interstimulus&#xD;
           intervals (ISIs).&#xD;
&#xD;
        -  Blink rate: number of eye blinks per minute.&#xD;
&#xD;
        -  LQs: the total score of the Light Questionnaire Scale.&#xD;
&#xD;
      These results will be compared between the two patient groups and HVs. We will look for&#xD;
      possible correlations between neurophysiological and clinical data.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Protocol could not be carried out to achieve the aims of the study&#xD;
  </why_stopped>
  <start_date type="Actual">October 30, 2017</start_date>
  <completion_date type="Actual">April 24, 2019</completion_date>
  <primary_completion_date type="Actual">April 24, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Photic blink reflex recovery cycle</measure>
    <time_frame>Single determination</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Electrocutaneous blink reflex recovery cycle; Blink rate; Light Questionnaire Scale</measure>
    <time_frame>Single determination</time_frame>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">17</enrollment>
  <condition>Blepharospasm</condition>
  <arm_group>
    <arm_group_label>Healthy</arm_group_label>
    <description>24 healthy volunteers (HVs)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Patients</arm_group_label>
    <description>24 patients with blepharospasm</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Patients 2</arm_group_label>
    <description>24 patients with increased blinking alone.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        We plan to recruit 24 patients with blepharospasm, 24 healthy volunteers (HVs) and 24&#xD;
        patients with increased blinking alone.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
          -  Must be 18 years or older&#xD;
&#xD;
          -  For patients only: fulfill the criteria of&#xD;
&#xD;
               -  Primary BPS (either focal or related to segmental dystonia) in accordance with&#xD;
                  published criteria or&#xD;
&#xD;
               -  Excessive involuntary eyelid closure without sustained OO spasms in accordance&#xD;
                  with Conte et al + having a resting blink rate above 15 blinks per minute.&#xD;
&#xD;
          -  Ability to give informed consent.&#xD;
&#xD;
          -  Ability to comply with all study procedures.&#xD;
&#xD;
          -  Agree to consume no caffeine or alcohol for 12 hours before participating in the&#xD;
             testing visits.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
        Any of the following will exclude PATIENTS from the study:&#xD;
&#xD;
          -  Secondary causes of excessive involuntary eyelid closure such as ophthalmologist&#xD;
             disorders involving the ocular surface, tear film, or eyelids.&#xD;
&#xD;
          -  Any evidence suggesting a psychogenic movement disorder such as persisting unilateral&#xD;
             or asymmetric symptoms, paroxysmal symptoms, and other inconsistencies such as pain,&#xD;
             associated somatizations, blinking diminished by distraction, unusual sensory tricks,&#xD;
             or unexpected response.&#xD;
&#xD;
          -  Botulinum toxin treatment &lt; 3 months prior to a testing visit.&#xD;
&#xD;
          -  History of chronic exposure (&gt;3 month) to dopamine receptor blocking agents before the&#xD;
             onset of increased blinking alone or BPS.&#xD;
&#xD;
        Any of the following will exclude BOTH patients and healthy controls from the study:&#xD;
&#xD;
          -  Has any major medical problem other than increased blinking or dystonia in patient&#xD;
             groups (such as decompensated chronic diseases or conditions that cause serious&#xD;
             disability such as congestive heart failure/NYHA score greater than or equal to 2,&#xD;
             severe COPD, advanced neoplasia, severe arthritis, HIV/AIDS, blindness).&#xD;
&#xD;
          -  Employees, staff or fellows of HMCS in NINDS.&#xD;
&#xD;
          -  Has used illegal drugs within the past 6 months based on history. The intent is to&#xD;
             exclude those with drug use that may affect study results.&#xD;
&#xD;
          -  Self-reported consumption of more than 7 alcoholic drinks a week in the case of a&#xD;
             woman and 14 alcoholic drinks a week in the case of a man.&#xD;
&#xD;
          -  Abnormal findings on neurologic exam (other than increased blinking or dystonia in&#xD;
             patient groups).&#xD;
&#xD;
          -  Presence of anatomical or functional eyelid abnormalities other than involuntary&#xD;
             eyelid closure or OOs spasms (including apraxia of eyelid opening, and other disorders&#xD;
             such as tics or tardive syndromes).&#xD;
&#xD;
          -  Has a neurologic disorder other than increased blinking or dystonia.&#xD;
&#xD;
          -  Has major depression or any major mental disorders (axis I disorders).&#xD;
&#xD;
          -  Has had a head injury where there was a loss of consciousness for more than a few&#xD;
             seconds.&#xD;
&#xD;
          -  Has a deep brain stimulator, pacemaker or other implantable electronic device subject&#xD;
             to malfunction by electrical stimulation.&#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>
  <overall_official>
    <last_name>Mark Hallett, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Institute of Neurological Disorders and Stroke (NINDS)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Adams WH, Digre KB, Patel BC, Anderson RL, Warner JE, Katz BJ. The evaluation of light sensitivity in benign essential blepharospasm. Am J Ophthalmol. 2006 Jul;142(1):82-87. doi: 10.1016/j.ajo.2006.02.020.</citation>
    <PMID>16815254</PMID>
  </reference>
  <reference>
    <citation>Albanese A, Bhatia K, Bressman SB, Delong MR, Fahn S, Fung VS, Hallett M, Jankovic J, Jinnah HA, Klein C, Lang AE, Mink JW, Teller JK. Phenomenology and classification of dystonia: a consensus update. Mov Disord. 2013 Jun 15;28(7):863-73. doi: 10.1002/mds.25475. Epub 2013 May 6.</citation>
    <PMID>23649720</PMID>
  </reference>
  <reference>
    <citation>Aramideh M, Eekhof JL, Bour LJ, Koelman JH, Speelman JD, Ongerboer de Visser BW. Electromyography and recovery of the blink reflex in involuntary eyelid closure: a comparative study. J Neurol Neurosurg Psychiatry. 1995 Jun;58(6):692-8. doi: 10.1136/jnnp.58.6.692. Erratum In: J Neurol Neurosurg Psychiatry 1995 Dec;59(6):662.</citation>
    <PMID>7608667</PMID>
  </reference>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>August 25, 2017</study_first_submitted>
  <study_first_submitted_qc>August 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 28, 2017</study_first_posted>
  <last_update_submitted>April 25, 2019</last_update_submitted>
  <last_update_submitted_qc>April 25, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 26, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Belpharospasm</keyword>
  <keyword>Blink Reflex</keyword>
  <keyword>Eyeblink</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Blepharospasm</mesh_term>
  </condition_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/NCT03263000
org study id: 170159
secondary id: 17-N-0159
nct id: NCT03263000
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Background:

      Some people who have increased blinking may later develop blepharospasm. Blepharospasm is a
      neurological disorder that causes involuntary closing of the eyes. Researchers want to learn
      more about how eyes close in response to different stimuli. They want to study this in
      healthy people, people with increased blinking, and people with blepharospasm.

      Objective:

      To learn how light exposure affects people with blepharospasm.

      Eligibility:

      People ages 18 and older with blepharospasm or increased blinking, and healthy volunteers

      Design:

      Participants will be screened with:

      Medical history

      Physical exam

      Neurological exam

      Participants will have up to 5 visits. The number of visits will depend on the number of
      tests they opt to have. They can opt to have up to 4 tests. Visits last 60-90 minutes. They
      cannot drink alcohol or caffeinated drinks for at least 12 hours before visits. Visits could
      include the following tests:

      Evaluation of eyelid movements. This will be video recorded.

      Electromyography: Small sticky electrodes are placed on the lower eyelid skin. These are
      attached to wires. Muscle activity is recorded during blink reflex procedures.

      Electrical stimulation: An electrode is placed close to the eyebrow. It will deliver small
      electrical shocks. The strength of the shocks will be enough to provoke a blink.

      Photic stimulation: A lamp is placed in front of the face. It will deliver single or paired
      flashes. The flashes will be at various intervals and intensities. Participants will wear a
      patch over one eye during this test.

      Combination of electrical and photic stimulation

      ...
Objective:

        -  The purpose of the first study of this protocol is to improve understanding of the role
           played by light sensitivity in the pathophysiology of blepharospasm (BPS).

        -  As a characteristic feature of BPS, the electrocutaneous blink reflex recovery cycle
           (EBR rc) shows an increased recovery index of R2 compared with healthy subjects.

        -  In the first study proposed under this protocol we will study the recovery cycle of the
           blink reflex evoked by a light stimulus (PBR rc) and the effect of a light stimulus on
           the EBR (MBR rc) in patient with BPS. Since photophobia and increased blinking are
           common symptoms in this group of patients, we will look for possible correlations
           between neurophysiological data and the Light Sensitivity Questionnaire (LSQ) or the
           Blink rate (Brt). The second study proposed under this protocol will explore the PBR rc
           and the MBR rc in patients with increased blinking alone, a condition indicated as a
           possible precursor of BPS.

      Study population:

      We plan to recruit 24 patients with blepharospasm, 24 healthy volunteers (HVs) and 24
      patients with increased blinking alone.

      Design:

      In two different studies, we will compare all the results from the EBR rc, PBR rc and MBR rc
      between BPS patients (first study) or increased blinking patients (second study) and HVs. We
      will also look for possible correlation between the neurophysiologic data and the clinical
      scales acquired during a clinical assessment. In the EBR rc procedure, the supraorbital nerve
      will be stimulated with paired electrical stimuli at varying ISIs and the EMG response from
      the orbicularis oculi muscles will be recorded. In the PBR rc procedure, paired light stimuli
      will be given at varying interstimulus intervals (ISIs) and the EMG responses from the
      orbicularis oculi will be recorded. In the MBR rc study a weak light stimulation will be
      given at varying ISIs before an electrical stimulation of the supraorbital nerve. Each
      experimental procedure will last about 1 hour. There will be one screening visit and up to 4
      testing visits per participant. However, participant can either undergo all the experimental
      procedures or participate in only some of them and will be allowed to participate in two
      experimental procedures per testing visit.

      Outcome measurements:

        -  EBR rc, PBR rc, MBR rc: the electromyography (EMG) responses at different interstimulus
           intervals (ISIs).

        -  Blink rate: number of eye blinks per minute.

        -  LQs: the total score of the Light Questionnaire Scale.

      These results will be compared between the two patient groups and HVs. We will look for
      possible correlations between neurophysiological and clinical data.
observational model: Case-Control
time perspective: Cross-Sectional
measure: Photic blink reflex recovery cycle
time frame: Single determination
measure: Electrocutaneous blink reflex recovery cycle; Blink rate; Light Questionnaire Scale
time frame: Single determination
arm group label: Healthy
description: 24 healthy volunteers (HVs)
arm group label: Patients
description: 24 patients with blepharospasm
arm group label: Patients 2
description: 24 patients with increased blinking alone.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Mark Hallett, M.D.
role: Principal Investigator
affiliation: National Institute of Neurological Disorders and Stroke (NINDS)
facility: 
country: United States
citation: Adams WH, Digre KB, Patel BC, Anderson RL, Warner JE, Katz BJ. The evaluation of light sensitivity in benign essential blepharospasm. Am J Ophthalmol. 2006 Jul;142(1):82-87. doi: 10.1016/j.ajo.2006.02.020.
PMID: 16815254
citation: Albanese A, Bhatia K, Bressman SB, Delong MR, Fahn S, Fung VS, Hallett M, Jankovic J, Jinnah HA, Klein C, Lang AE, Mink JW, Teller JK. Phenomenology and classification of dystonia: a consensus update. Mov Disord. 2013 Jun 15;28(7):863-73. doi: 10.1002/mds.25475. Epub 2013 May 6.
PMID: 23649720
citation: Aramideh M, Eekhof JL, Bour LJ, Koelman JH, Speelman JD, Ongerboer de Visser BW. Electromyography and recovery of the blink reflex in involuntary eyelid closure: a comparative study. J Neurol Neurosurg Psychiatry. 1995 Jun;58(6):692-8. doi: 10.1136/jnnp.58.6.692. Erratum In: J Neurol Neurosurg Psychiatry 1995 Dec;59(6):662.
PMID: 7608667
responsible party type: Sponsor
mesh term: Blepharospasm