<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/NCT03818204</url>
  </required_header>
  <id_info>
    <org_study_id>18-166H</org_study_id>
    <nct_id>NCT03818204</nct_id>
  </id_info>
  <brief_title>Clinical Trial to Improve the Magnetic Levator Prosthesis</brief_title>
  <official_title>Clinical Trial to Improve the Magnetic Levator Prosthesis (MLP) Including the Development and Testing of a Novel Adjustable Force System</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts Eye and Ear Infirmary</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>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Blepharoptosis (incomplete opening of the eyelids) occurs because of a disruption in the&#xD;
      normal agonist-antagonist neuro-muscular complex balance. An external device could restore&#xD;
      eyelid movement. A newer class of permanent magnets made of alloys of neodymium (Nd), iron&#xD;
      (Fe) and boron (B) might provide the technology needed to develop a feasible external&#xD;
      magnetic device that could restore eyelid movement.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Blepharoptosis (incomplete opening of the eyelids) occurs because of a disruption in the&#xD;
      normal agonist-antagonist neuro-muscular complex balance. An external device, if able to&#xD;
      generate an appropriately balanced force, could restore eyelid movement by performing the&#xD;
      paralyzed function; for example, a ptotic (droopy) eyelid could be opened, and the&#xD;
      functioning eyelid closure muscle could overcome the device's force (Conway, 1973; Barmettler&#xD;
      et. al, 2014; Houston et. al, 2014). Despite this seemingly straight-forward application,&#xD;
      permanent magnets for eyelid movement disorders have not thus far become an available&#xD;
      treatment. It is possible that earlier magnetic materials lacked the strength (at sizes which&#xD;
      were acceptable to patients) to effectively restore the blink, or methods of implantation or&#xD;
      external mounting were not effective. A newer class of permanent magnets made of alloys of&#xD;
      neodymium (Nd), iron (Fe) and boron (B) might provide the technology needed to develop a&#xD;
      feasible external magnetic device. They generate the strongest static magnetic fields yet&#xD;
      possible, (1.3T compared to 0.4T of conventional ferrite magnets) (Cyrot, 2005) with&#xD;
      exceptional uniaxial magnetocrystalline anisotropy, which makes them resistive to&#xD;
      demagnetization (Chikazumui, 1997). The increased magnetic force at a fraction of the size&#xD;
      has led to attempts for other medical applications including implantation for&#xD;
      gastroesophageal reflux disease (Ganz, 2013), in dental prosthetics (Uribe, 2006), ocular&#xD;
      reconstructive surgery (de Negreiros, 2012), and glaucoma (Paschalis et. al, 2013). Problems&#xD;
      with extended external non-surgical adhesion to the skin of the eyelid may be solved with&#xD;
      hydrocolloid-based medical adhesives e.g. Tegaderm™ (Chen, 1997), already used for IV&#xD;
      catheter securement, wound dressing, and as a protective eye covering (FDA, 1997). This&#xD;
      material is extremely thin, transparent, and oxygen permeable with an established safety&#xD;
      profile for days to weeks of wear. The hydrophyllic properties (FDA, 1997) may be beneficial&#xD;
      to the eyelids, which are often moist. In our prior work we established proof-of-concept data&#xD;
      demonstrating safety and efficacy for temporary management ptosis up to 2 hour per day for 2&#xD;
      weeks. Due to the sensitive force distance relationship characteristics of magnetic fields&#xD;
      and variable nature of ptosis (often worsens throughout the day) the MLP required frequent&#xD;
      readjustment and consistent correction was difficult to achieve. Other challenges included&#xD;
      lid redness with longer wear times (in the participants who wore the MLP longer than&#xD;
      instructed), incomplete spontaneous blinking, and difficultly with self-application of the&#xD;
      magnetic lid array to the eye lid. This study aims to address these challenges. In order to&#xD;
      improve the MLP we will determine the range of force in the target severe ptosis population&#xD;
      to open the lid and where blinking is inhibited, determine the best polarity combination&#xD;
      between the lid magnets and the spectacle magnet, determine if rotating the spectacle magnet&#xD;
      is a good method to allow simple force adjustment via a dial on the side of the frame,&#xD;
      determine if custom made frames improve stability of the frame, and create an applicator tool&#xD;
      to help participants apply the lid magnet themselves.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">February 7, 2019</start_date>
  <completion_date type="Anticipated">July 2023</completion_date>
  <primary_completion_date type="Anticipated">July 2023</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>Crossover Assignment</intervention_model>
    <intervention_model_description>This is a prospective cross-over study with some aims having double-blind methodology. Randomization and masking will be used in aims 1 and 2 experiments. Aim 1: The spectacle magnet will be rotated to 1 of 4 settings in an order which will be counterbalanced using a Latin Square approach. Patient and experimenters will be masked to the actual force setting. Aim 2: 15 participants will be randomized to be fitted first with either through thickness or through height polarization of the lid magnets using an online randomizer by a study staff not involved in the data collection or analysis who will keep the code. Every other subject in the sequence will be balanced to receive the alternative order. Counterbalancing is being used because of the small sample size.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Investigator)</masking>
    <masking_description>Masked/blinded clinical staff will apply the lid magnets polarized either through thickness or through height (counterbalanced) to the study subjects. Also, 10 magnets of different sizes will be placed inside a plastic housing in order to prevent bias (participant and clinical staff will not know the actual size of the magnets) and counterbalance to control for order effect.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in interpalpebral fissure during eye opening</measure>
    <time_frame>This outcome will be analysed by reviewing video recording. Video recording will be performed 7 times for the duration of the study (4 videos performed during visit 1; 3 video performed during visit 2)</time_frame>
    <description>A &gt; 1mm change in interpalpebral fissure (resting open) at min and max force of the rotatable system; a &gt;1mm change in interpalpebral fissure when the lid array is polarized through thickness as compared to through height.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in interpalpebral fissure during the blink</measure>
    <time_frame>Video recording will be performed 7 times for the duration of the study (4 videos performed during visit 1; 3 video performed during visit 2)</time_frame>
    <description>Video analysis to measure the completeness of eye closure with the MLP compared to 1) no device, 2) relative to the contralateral side (if normal), 3) relative to different configurations of the device and custom vs. non-custom frames.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Blepharoptosis</condition>
  <condition>Ptosis, Eyelid</condition>
  <condition>Myasthenia Gravis</condition>
  <condition>Stroke</condition>
  <condition>Traumatic Brain Injury</condition>
  <arm_group>
    <arm_group_label>Experimental Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The purpose of the experimental group is to test the intervention. Participants will have their acuity measured (refraction as needed), slit lamp with Nafl &amp; NEI scale, visual functioning questionnaire (VFQ), cognitive assessment (MOCA).The eye lid will be prepped and video recorded.The masked clinical staff will then apply the polarized magnets and perform a number of measurements to ascertain effectiveness of intervention.&#xD;
-Intervention - Magnetic Levator Prosthesis (MLP)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control/Normal Vision Group</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>The purpose of the normal vision group is to test the experimental setup prior to enrolling ptosis patients. If the measurements of the normal vision group are found to be non-different to the experimental group, the data will be pooled.&#xD;
-Intervention - Magnetic Levator Prosthesis (MLP)</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Magnetic Levator Prosthesis (MLP)</intervention_name>
    <description>Neodymium magnet embedded in a glasses frame and a polymer embedded (PDMS) micro-magnet array fitted externally to the upper lid with IV 3000 securement film. The IV 3000 is FDA approved for extended wear on the skin. Tegaderm, which is essentially the same adhesive, is even FDA approved as an eye covering (we used Tegaderm in early studies but switched to IV 3000 for its superior ease of handling based on packaging technique).</description>
    <arm_group_label>Control/Normal Vision Group</arm_group_label>
    <arm_group_label>Experimental Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Experimental:&#xD;
&#xD;
          -  Presence of ptosis for at least one eye which obscures the visual axis in the resting&#xD;
             position (without frontalis drive, lifting with forehead muscles)&#xD;
&#xD;
          -  Moderate cognitive function or better defined as greater than or equal to 18 out of 30&#xD;
             on a pre-screening of the Mini-Mental State Exam&#xD;
&#xD;
          -  Age 5 or older&#xD;
&#xD;
          -  Control/Normal Vision Group:&#xD;
&#xD;
          -  Absence of ptosis which obscures the visual axis&#xD;
&#xD;
          -  Age 18 or older&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Experimental:&#xD;
&#xD;
          -  Absence of blepharoptosis or presence of a corneal ulcer.&#xD;
&#xD;
          -  Those with a corneal ulcer are at risk for permanent loss of vision and should be&#xD;
             managed with proven methods.&#xD;
&#xD;
          -  Age less than 5,&#xD;
&#xD;
          -  Severe Cognitive impairment defined as MMSE score &lt;18, behaviors consistent with&#xD;
             delirium (combinations of disorientation, hallucinations, delusions, and incoherent&#xD;
             speech), or lethargy. These individuals must be excluded since participation requires&#xD;
             competent self-care, reliable responses and cooperation during fitting of the devices.&#xD;
&#xD;
          -  Control/Normal Vision Group:&#xD;
&#xD;
          -  Presence of Blepharoptosis&#xD;
&#xD;
          -  Age less than 18&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>4 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kevin Houston, OD, M. Sc.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mass Eye and Ear</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Schepens Eye Research Institute</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>April 2022</verification_date>
  <study_first_submitted>January 23, 2019</study_first_submitted>
  <study_first_submitted_qc>January 23, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <last_update_submitted>April 4, 2022</last_update_submitted>
  <last_update_submitted_qc>April 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 6, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts Eye and Ear Infirmary</investigator_affiliation>
    <investigator_full_name>Kevin Houston</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>Myasthenia Gravis</mesh_term>
    <mesh_term>Brain Injuries</mesh_term>
    <mesh_term>Brain Injuries, Traumatic</mesh_term>
    <mesh_term>Blepharoptosis</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/NCT03818204
org study id: 18-166H
nct id: NCT03818204
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Blepharoptosis (incomplete opening of the eyelids) occurs because of a disruption in the
      normal agonist-antagonist neuro-muscular complex balance. An external device could restore
      eyelid movement. A newer class of permanent magnets made of alloys of neodymium (Nd), iron
      (Fe) and boron (B) might provide the technology needed to develop a feasible external
      magnetic device that could restore eyelid movement.
Blepharoptosis (incomplete opening of the eyelids) occurs because of a disruption in the
      normal agonist-antagonist neuro-muscular complex balance. An external device, if able to
      generate an appropriately balanced force, could restore eyelid movement by performing the
      paralyzed function; for example, a ptotic (droopy) eyelid could be opened, and the
      functioning eyelid closure muscle could overcome the device's force (Conway, 1973; Barmettler
      et. al, 2014; Houston et. al, 2014). Despite this seemingly straight-forward application,
      permanent magnets for eyelid movement disorders have not thus far become an available
      treatment. It is possible that earlier magnetic materials lacked the strength (at sizes which
      were acceptable to patients) to effectively restore the blink, or methods of implantation or
      external mounting were not effective. A newer class of permanent magnets made of alloys of
      neodymium (Nd), iron (Fe) and boron (B) might provide the technology needed to develop a
      feasible external magnetic device. They generate the strongest static magnetic fields yet
      possible, (1.3T compared to 0.4T of conventional ferrite magnets) (Cyrot, 2005) with
      exceptional uniaxial magnetocrystalline anisotropy, which makes them resistive to
      demagnetization (Chikazumui, 1997). The increased magnetic force at a fraction of the size
      has led to attempts for other medical applications including implantation for
      gastroesophageal reflux disease (Ganz, 2013), in dental prosthetics (Uribe, 2006), ocular
      reconstructive surgery (de Negreiros, 2012), and glaucoma (Paschalis et. al, 2013). Problems
      with extended external non-surgical adhesion to the skin of the eyelid may be solved with
      hydrocolloid-based medical adhesives e.g. Tegaderm™ (Chen, 1997), already used for IV
      catheter securement, wound dressing, and as a protective eye covering (FDA, 1997). This
      material is extremely thin, transparent, and oxygen permeable with an established safety
      profile for days to weeks of wear. The hydrophyllic properties (FDA, 1997) may be beneficial
      to the eyelids, which are often moist. In our prior work we established proof-of-concept data
      demonstrating safety and efficacy for temporary management ptosis up to 2 hour per day for 2
      weeks. Due to the sensitive force distance relationship characteristics of magnetic fields
      and variable nature of ptosis (often worsens throughout the day) the MLP required frequent
      readjustment and consistent correction was difficult to achieve. Other challenges included
      lid redness with longer wear times (in the participants who wore the MLP longer than
      instructed), incomplete spontaneous blinking, and difficultly with self-application of the
      magnetic lid array to the eye lid. This study aims to address these challenges. In order to
      improve the MLP we will determine the range of force in the target severe ptosis population
      to open the lid and where blinking is inhibited, determine the best polarity combination
      between the lid magnets and the spectacle magnet, determine if rotating the spectacle magnet
      is a good method to allow simple force adjustment via a dial on the side of the frame,
      determine if custom made frames improve stability of the frame, and create an applicator tool
      to help participants apply the lid magnet themselves.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: This is a prospective cross-over study with some aims having double-blind methodology. Randomization and masking will be used in aims 1 and 2 experiments. Aim 1: The spectacle magnet will be rotated to 1 of 4 settings in an order which will be counterbalanced using a Latin Square approach. Patient and experimenters will be masked to the actual force setting. Aim 2: 15 participants will be randomized to be fitted first with either through thickness or through height polarization of the lid magnets using an online randomizer by a study staff not involved in the data collection or analysis who will keep the code. Every other subject in the sequence will be balanced to receive the alternative order. Counterbalancing is being used because of the small sample size.
primary purpose: Treatment
masking: Single (Investigator)
masking description: Masked/blinded clinical staff will apply the lid magnets polarized either through thickness or through height (counterbalanced) to the study subjects. Also, 10 magnets of different sizes will be placed inside a plastic housing in order to prevent bias (participant and clinical staff will not know the actual size of the magnets) and counterbalance to control for order effect.
measure: Change in interpalpebral fissure during eye opening
time frame: This outcome will be analysed by reviewing video recording. Video recording will be performed 7 times for the duration of the study (4 videos performed during visit 1; 3 video performed during visit 2)
description: A > 1mm change in interpalpebral fissure (resting open) at min and max force of the rotatable system; a >1mm change in interpalpebral fissure when the lid array is polarized through thickness as compared to through height.
measure: Change in interpalpebral fissure during the blink
time frame: Video recording will be performed 7 times for the duration of the study (4 videos performed during visit 1; 3 video performed during visit 2)
description: Video analysis to measure the completeness of eye closure with the MLP compared to 1) no device, 2) relative to the contralateral side (if normal), 3) relative to different configurations of the device and custom vs. non-custom frames.
arm group label: Experimental Group
arm group type: Experimental
description: The purpose of the experimental group is to test the intervention. Participants will have their acuity measured (refraction as needed), slit lamp with Nafl & NEI scale, visual functioning questionnaire (VFQ), cognitive assessment (MOCA).The eye lid will be prepped and video recorded.The masked clinical staff will then apply the polarized magnets and perform a number of measurements to ascertain effectiveness of intervention.
-Intervention - Magnetic Levator Prosthesis (MLP)
arm group label: Control/Normal Vision Group
arm group type: Other
description: The purpose of the normal vision group is to test the experimental setup prior to enrolling ptosis patients. If the measurements of the normal vision group are found to be non-different to the experimental group, the data will be pooled.
-Intervention - Magnetic Levator Prosthesis (MLP)
intervention type: Device
intervention name: Magnetic Levator Prosthesis (MLP)
description: Neodymium magnet embedded in a glasses frame and a polymer embedded (PDMS) micro-magnet array fitted externally to the upper lid with IV 3000 securement film. The IV 3000 is FDA approved for extended wear on the skin. Tegaderm, which is essentially the same adhesive, is even FDA approved as an eye covering (we used Tegaderm in early studies but switched to IV 3000 for its superior ease of handling based on packaging technique).
arm group label: Control/Normal Vision Group
arm group label: Experimental Group
criteria: 
gender: All
minimum age: 4 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Kevin Houston, OD, M. Sc.
role: Principal Investigator
affiliation: Mass Eye and Ear
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Massachusetts Eye and Ear Infirmary
investigator full name: Kevin Houston
investigator title: Assistant Professor of Ophthalmology
mesh term: Myasthenia Gravis
mesh term: Brain Injuries
mesh term: Brain Injuries, Traumatic
mesh term: Blepharoptosis