<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/NCT01691651</url>
  </required_header>
  <id_info>
    <org_study_id>RECUNIFESP-87051</org_study_id>
    <nct_id>NCT01691651</nct_id>
  </id_info>
  <brief_title>Botulinum Toxin A for the Treatment of Keratoconus</brief_title>
  <official_title>Botulinum Toxin Type A for Keratoconus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Federal University of São Paulo</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Federal University of São Paulo</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to associate the use of botulinum toxin type A for patients with&#xD;
      keratoconus to demonstrate that tension eyelid has an important role in disease progression.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Subcutaneous injection of botulinum toxin type A will be performed at two points in a nasal&#xD;
      and temporal extent of the orbicularis muscle of a group of patients with keratoconus&#xD;
      (Botulinum toxin A group).The idea is to evaluate the change in palpebral fissure in patients&#xD;
      from group botulinum toxin A over a period of 18 months.The measurements of the palpebral&#xD;
      fissure will be performed by the Image J (version 1.34s) program, developed by the National&#xD;
      Institutes of Health (USA).The unit of measure is the millimetre.The patients of the&#xD;
      botulinum toxin A group will be compared with a control group, without any intervention.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">October 2014</completion_date>
  <primary_completion_date type="Actual">October 2014</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Measurement of the palpebral fissure</measure>
    <time_frame>Eighteen months.</time_frame>
    <description>We will evaluate the change in palpebral fissure (unit of measure=millimetre)by 18 months.These time points will be included:baseline, 3, 6, 12 and 18 months.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Corneal topography</measure>
    <time_frame>Eighteen months.</time_frame>
    <description>We will evaluate corneal topography [flattest keratometry, steepest keratometry and average keratometry(unit of measure=diopters)]by 18 months.These time points will be included:baseline, 3, 6,12 and 18 months.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Corrected visual acuity</measure>
    <time_frame>Eighteen months.</time_frame>
    <description>We will evaluate the corrected visual acuity (unit of measure=logMAR)by 18 months.These time points will be included:baseline, 3, 6, 12 and 18 months.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Keratoconus</condition>
  <arm_group>
    <arm_group_label>Botulinum toxin type A</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The group that will be subjected to the injection of botulinum toxin (subcutaneous injection of botulinum toxin type A).Subcutaneous botulinum toxin A injection will be performed in this group, (2.5 units per point application), at two points in a nasal and temporal extent of the orbicularis muscle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>The group that will not be subjected to any intervention.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Subcutaneous injection of botulinum toxin type A</intervention_name>
    <description>Subcutaneous injection of botulinum toxin type A (2.5 units per application point) at two points in a nasal and temporal extent of the orbicularis muscle will be performed in the Botulinum toxin type A group.</description>
    <arm_group_label>Botulinum toxin type A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Botulinum Toxin Type A</intervention_name>
    <description>2.5 units per point of application at two points in a nasal and temporal extent of the orbicularis muscle.</description>
    <arm_group_label>Botulinum toxin type A</arm_group_label>
    <other_name>Botox (Allergan)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  patients with documented keratoconus&#xD;
&#xD;
          -  best-corrected visual acuity measurable at refraction test&#xD;
&#xD;
          -  age between 10-40 years&#xD;
&#xD;
          -  good health&#xD;
&#xD;
          -  understand the procedure and its limitations&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  only one functional eye&#xD;
&#xD;
          -  previous ocular surgery&#xD;
&#xD;
          -  concurrent corneal infection and other ocular diseases that modified the visual acuity&#xD;
&#xD;
          -  known allergy to botulinum toxin&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  poor collaboration for performing the examinations and the procedure&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>10 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Adimara C Renesto, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Federal University of São Paulo</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Teissy H Osaki, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Federal University of São Paulo</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Midori H Osaki, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Federal University of São Paulo</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Mauro Q Campos, MD</last_name>
    <role>Study Director</role>
    <affiliation>Federal University of São Paulo</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Federal University of São Paulo, Department of Ophthalmology</name>
      <address>
        <city>São Paulo</city>
        <zip>04023-062</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <link>
    <url>http://pubmed.gov</url>
    <description>Pubmed comprises citations for biomedical literature from MEDLINE, life science journals, and online books.</description>
  </link>
  <reference>
    <citation>Rabinowitz YS. Keratoconus. Surv Ophthalmol. 1998 Jan-Feb;42(4):297-319. doi: 10.1016/s0039-6257(97)00119-7.</citation>
    <PMID>9493273</PMID>
  </reference>
  <reference>
    <citation>Edwards M, McGhee CN, Dean S. The genetics of keratoconus. Clin Exp Ophthalmol. 2001 Dec;29(6):345-51. doi: 10.1046/j.1442-9071.2001.d01-16.x.</citation>
    <PMID>11778802</PMID>
  </reference>
  <reference>
    <citation>Miranda D, Sartori M, Francesconi C, Allemann N, Ferrara P, Campos M. Ferrara intrastromal corneal ring segments for severe keratoconus. J Refract Surg. 2003 Nov-Dec;19(6):645-53. doi: 10.3928/1081-597X-20031101-06.</citation>
    <PMID>14640429</PMID>
  </reference>
  <reference>
    <citation>Kymionis GD, Kontadakis GA, Kounis GA, Portaliou DM, Karavitaki AE, Magarakis M, Yoo S, Pallikaris IG. Simultaneous topography-guided PRK followed by corneal collagen cross-linking for keratoconus. J Refract Surg. 2009 Sep;25(9):S807-11. doi: 10.3928/1081597X-20090813-09. Epub 2009 Sep 11.</citation>
    <PMID>19772256</PMID>
  </reference>
  <reference>
    <citation>Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003 May;135(5):620-7. doi: 10.1016/s0002-9394(02)02220-1.</citation>
    <PMID>12719068</PMID>
  </reference>
  <reference>
    <citation>Renesto Ada C, Melo LA Jr, Sartori Mde F, Campos M. Sequential topical riboflavin with or without ultraviolet a radiation with delayed intracorneal ring segment insertion for keratoconus. Am J Ophthalmol. 2012 May;153(5):982-993.e3. doi: 10.1016/j.ajo.2011.10.014. Epub 2012 Jan 20.</citation>
    <PMID>22265143</PMID>
  </reference>
  <reference>
    <citation>Bawazeer AM, Hodge WG, Lorimer B. Atopy and keratoconus: a multivariate analysis. Br J Ophthalmol. 2000 Aug;84(8):834-6. doi: 10.1136/bjo.84.8.834.</citation>
    <PMID>10906086</PMID>
  </reference>
  <reference>
    <citation>Kim T, Khosla-Gupta B, Debacker C. Blepharoptosis-induced superior keratoconus. Am J Ophthalmol. 2000 Aug;130(2):232-4. doi: 10.1016/s0002-9394(00)00497-9.</citation>
    <PMID>11004300</PMID>
  </reference>
  <reference>
    <citation>Parunovic A. Floppy eyelid syndrome. Br J Ophthalmol. 1983 Apr;67(4):264-6. doi: 10.1136/bjo.67.4.264.</citation>
    <PMID>6830745</PMID>
  </reference>
  <reference>
    <citation>Brown IA. Ankyloblepharon associated with keratoconus. Br J Ophthalmol. 1967 Feb;51(2):138-9. doi: 10.1136/bjo.51.2.138. No abstract available.</citation>
    <PMID>6018907</PMID>
  </reference>
  <reference>
    <citation>Cristina Kenney M, Brown DJ. The cascade hypothesis of keratoconus. Cont Lens Anterior Eye. 2003 Sep;26(3):139-46. doi: 10.1016/S1367-0484(03)00022-5.</citation>
    <PMID>16303509</PMID>
  </reference>
  <reference>
    <citation>Scott AB, Kennedy RA, Stubbs HA. Botulinum A toxin injection as a treatment for blepharospasm. Arch Ophthalmol. 1985 Mar;103(3):347-50. doi: 10.1001/archopht.1985.01050030043017.</citation>
    <PMID>3977705</PMID>
  </reference>
  <reference>
    <citation>Schellini SA, Matai O, Igami TZ, Padovani CR, Padovani CP. [Essential blepharospasm and hemifacial spasm: characteristic of the patient, botulinum toxin A treatment and literature review]. Arq Bras Oftalmol. 2006 Jan-Feb;69(1):23-6. doi: 10.1590/s0004-27492006000100005. Epub 2006 Feb 10. Portuguese.</citation>
    <PMID>16491229</PMID>
  </reference>
  <reference>
    <citation>Nicoletti AG, Aoki L, Nahas TR, Matayoshi S. [Essential blepharospasm: literature review]. Arq Bras Oftalmol. 2010 Sep-Oct;73(5):469-73. doi: 10.1590/s0004-27492010000500018. Portuguese.</citation>
    <PMID>21225137</PMID>
  </reference>
  <reference>
    <citation>Coscarelli JM. Essential blepharospasm. Semin Ophthalmol. 2010 May;25(3):104-8. doi: 10.3109/08820538.2010.488564.</citation>
    <PMID>20590421</PMID>
  </reference>
  <reference>
    <citation>Krumeich JH, Daniel J, Knulle A. Live-epikeratophakia for keratoconus. J Cataract Refract Surg. 1998 Apr;24(4):456-63. doi: 10.1016/s0886-3350(98)80284-8.</citation>
    <PMID>9584238</PMID>
  </reference>
  <verification_date>October 2014</verification_date>
  <study_first_submitted>September 18, 2012</study_first_submitted>
  <study_first_submitted_qc>September 21, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2012</study_first_posted>
  <last_update_submitted>October 18, 2014</last_update_submitted>
  <last_update_submitted_qc>October 18, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 21, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Federal University of São Paulo</investigator_affiliation>
    <investigator_full_name>Adimara da Candelaria Renesto</investigator_full_name>
    <investigator_title>MD</investigator_title>
  </responsible_party>
  <keyword>Keratoconus</keyword>
  <keyword>Tetanus toxin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Keratoconus</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Botulinum Toxins</mesh_term>
    <mesh_term>Botulinum Toxins, Type A</mesh_term>
    <mesh_term>abobotulinumtoxinA</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/NCT01691651
org study id: RECUNIFESP-87051
nct id: NCT01691651
lead sponsor: 
has dmc: Yes
The purpose of this study is to associate the use of botulinum toxin type A for patients with
      keratoconus to demonstrate that tension eyelid has an important role in disease progression.
Subcutaneous injection of botulinum toxin type A will be performed at two points in a nasal
      and temporal extent of the orbicularis muscle of a group of patients with keratoconus
      (Botulinum toxin A group).The idea is to evaluate the change in palpebral fissure in patients
      from group botulinum toxin A over a period of 18 months.The measurements of the palpebral
      fissure will be performed by the Image J (version 1.34s) program, developed by the National
      Institutes of Health (USA).The unit of measure is the millimetre.The patients of the
      botulinum toxin A group will be compared with a control group, without any intervention.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Measurement of the palpebral fissure
time frame: Eighteen months.
description: We will evaluate the change in palpebral fissure (unit of measure=millimetre)by 18 months.These time points will be included:baseline, 3, 6, 12 and 18 months.
measure: Corneal topography
time frame: Eighteen months.
description: We will evaluate corneal topography [flattest keratometry, steepest keratometry and average keratometry(unit of measure=diopters)]by 18 months.These time points will be included:baseline, 3, 6,12 and 18 months.
measure: Corrected visual acuity
time frame: Eighteen months.
description: We will evaluate the corrected visual acuity (unit of measure=logMAR)by 18 months.These time points will be included:baseline, 3, 6, 12 and 18 months.
arm group label: Botulinum toxin type A
arm group type: Active Comparator
description: The group that will be subjected to the injection of botulinum toxin (subcutaneous injection of botulinum toxin type A).Subcutaneous botulinum toxin A injection will be performed in this group, (2.5 units per point application), at two points in a nasal and temporal extent of the orbicularis muscle.
arm group label: Control
arm group type: No Intervention
description: The group that will not be subjected to any intervention.
intervention type: Procedure
intervention name: Subcutaneous injection of botulinum toxin type A
description: Subcutaneous injection of botulinum toxin type A (2.5 units per application point) at two points in a nasal and temporal extent of the orbicularis muscle will be performed in the Botulinum toxin type A group.
arm group label: Botulinum toxin type A
intervention type: Drug
intervention name: Botulinum Toxin Type A
description: 2.5 units per point of application at two points in a nasal and temporal extent of the orbicularis muscle.
arm group label: Botulinum toxin type A
other name: Botox (Allergan)
criteria: 
gender: All
minimum age: 10 Years
maximum age: 40 Years
healthy volunteers: No
last name: Adimara C Renesto, MD
role: Principal Investigator
affiliation: Federal University of São Paulo
last name: Teissy H Osaki, MD
role: Study Chair
affiliation: Federal University of São Paulo
last name: Midori H Osaki, MD
role: Study Chair
affiliation: Federal University of São Paulo
last name: Mauro Q Campos, MD
role: Study Director
affiliation: Federal University of São Paulo
facility: 
country: Brazil
url: http://pubmed.gov
description: Pubmed comprises citations for biomedical literature from MEDLINE, life science journals, and online books.
citation: Rabinowitz YS. Keratoconus. Surv Ophthalmol. 1998 Jan-Feb;42(4):297-319. doi: 10.1016/s0039-6257(97)00119-7.
PMID: 9493273
citation: Edwards M, McGhee CN, Dean S. The genetics of keratoconus. Clin Exp Ophthalmol. 2001 Dec;29(6):345-51. doi: 10.1046/j.1442-9071.2001.d01-16.x.
PMID: 11778802
citation: Miranda D, Sartori M, Francesconi C, Allemann N, Ferrara P, Campos M. Ferrara intrastromal corneal ring segments for severe keratoconus. J Refract Surg. 2003 Nov-Dec;19(6):645-53. doi: 10.3928/1081-597X-20031101-06.
PMID: 14640429
citation: Kymionis GD, Kontadakis GA, Kounis GA, Portaliou DM, Karavitaki AE, Magarakis M, Yoo S, Pallikaris IG. Simultaneous topography-guided PRK followed by corneal collagen cross-linking for keratoconus. J Refract Surg. 2009 Sep;25(9):S807-11. doi: 10.3928/1081597X-20090813-09. Epub 2009 Sep 11.
PMID: 19772256
citation: Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003 May;135(5):620-7. doi: 10.1016/s0002-9394(02)02220-1.
PMID: 12719068
citation: Renesto Ada C, Melo LA Jr, Sartori Mde F, Campos M. Sequential topical riboflavin with or without ultraviolet a radiation with delayed intracorneal ring segment insertion for keratoconus. Am J Ophthalmol. 2012 May;153(5):982-993.e3. doi: 10.1016/j.ajo.2011.10.014. Epub 2012 Jan 20.
PMID: 22265143
citation: Bawazeer AM, Hodge WG, Lorimer B. Atopy and keratoconus: a multivariate analysis. Br J Ophthalmol. 2000 Aug;84(8):834-6. doi: 10.1136/bjo.84.8.834.
PMID: 10906086
citation: Kim T, Khosla-Gupta B, Debacker C. Blepharoptosis-induced superior keratoconus. Am J Ophthalmol. 2000 Aug;130(2):232-4. doi: 10.1016/s0002-9394(00)00497-9.
PMID: 11004300
citation: Parunovic A. Floppy eyelid syndrome. Br J Ophthalmol. 1983 Apr;67(4):264-6. doi: 10.1136/bjo.67.4.264.
PMID: 6830745
citation: Brown IA. Ankyloblepharon associated with keratoconus. Br J Ophthalmol. 1967 Feb;51(2):138-9. doi: 10.1136/bjo.51.2.138. No abstract available.
PMID: 6018907
citation: Cristina Kenney M, Brown DJ. The cascade hypothesis of keratoconus. Cont Lens Anterior Eye. 2003 Sep;26(3):139-46. doi: 10.1016/S1367-0484(03)00022-5.
PMID: 16303509
citation: Scott AB, Kennedy RA, Stubbs HA. Botulinum A toxin injection as a treatment for blepharospasm. Arch Ophthalmol. 1985 Mar;103(3):347-50. doi: 10.1001/archopht.1985.01050030043017.
PMID: 3977705
citation: Schellini SA, Matai O, Igami TZ, Padovani CR, Padovani CP. [Essential blepharospasm and hemifacial spasm: characteristic of the patient, botulinum toxin A treatment and literature review]. Arq Bras Oftalmol. 2006 Jan-Feb;69(1):23-6. doi: 10.1590/s0004-27492006000100005. Epub 2006 Feb 10. Portuguese.
PMID: 16491229
citation: Nicoletti AG, Aoki L, Nahas TR, Matayoshi S. [Essential blepharospasm: literature review]. Arq Bras Oftalmol. 2010 Sep-Oct;73(5):469-73. doi: 10.1590/s0004-27492010000500018. Portuguese.
PMID: 21225137
citation: Coscarelli JM. Essential blepharospasm. Semin Ophthalmol. 2010 May;25(3):104-8. doi: 10.3109/08820538.2010.488564.
PMID: 20590421
citation: Krumeich JH, Daniel J, Knulle A. Live-epikeratophakia for keratoconus. J Cataract Refract Surg. 1998 Apr;24(4):456-63. doi: 10.1016/s0886-3350(98)80284-8.
PMID: 9584238
responsible party type: Principal Investigator
investigator affiliation: Federal University of São Paulo
investigator full name: Adimara da Candelaria Renesto
investigator title: MD
mesh term: Keratoconus
mesh term: Botulinum Toxins
mesh term: Botulinum Toxins, Type A
mesh term: abobotulinumtoxinA