<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/NCT03823170</url>
  </required_header>
  <id_info>
    <org_study_id>MCCF-230784-RM</org_study_id>
    <nct_id>NCT03823170</nct_id>
  </id_info>
  <brief_title>Laser Therapy and Flouride Therapy in Desensibilization Hypomineralized Teeth</brief_title>
  <acronym>LTAFTIDHT</acronym>
  <official_title>Effectiveness of Laser Therapy Associated With Fluoride Therapy in Hypomineralized Teeth Desensibilization: Randomized Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universidade Ceuma</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Fundação de Amparo à Pesquisa e Desenvolvimento Científico do Maranhão</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Universidade Ceuma</source>
  <oversight_info>
    <has_dmc>Yes</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>
      To investigate the efficacy of laser therapy associated with fluorotherapy in the&#xD;
      desensibitization of hypomineralized teeth in children 8 to 12 years of age. A randomized&#xD;
      blinded clinical trial will be conducted. The instruments used will be a questionnaire&#xD;
      general, clinical examination, dental air syringe (evaluation of dental sensitivity) and&#xD;
      visual analogue scale (evaluation of the magnitude of dental sensitivity). Teeth with&#xD;
      hypomineralization molar-incisor (HMI) and the results of sensitivity and magnitude of dental&#xD;
      pain before and after the treatments will be recorded in a clinical record. The study groups&#xD;
      will be: treatment with laser therapy (Group 1); treatment with fluorotherapy (Group 2) and&#xD;
      treatment with laser therapy and fluorotherapy (Group 3).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      A blinded randomized clinical trial will be conducted. The study will be conducted with&#xD;
      children attending the Pediatric Dentistry Clinic of the Florence Institute's undergraduate&#xD;
      course, in São Luís, Maranhão, Brazil. As inclusion criteria, children from 8 to 12 years of&#xD;
      age will be adopted, with at least one first permanent or incisive erupted incisor (with&#xD;
      occlusal / incisal surface free of gingiva) present in the oral cavity and presenting&#xD;
      sensitive hypomineralization lesions. Exclusion criteria will be children with enamel&#xD;
      malformations linked to syndromes, with dental fluorosis, enamel hypoplasia or with imperfect&#xD;
      amelogenesis, teeth with loss of structure dental and carious lesions, children in&#xD;
      orthodontic treatment, children with cognition problems, children who used any type of&#xD;
      analgesic / anti-inflammatory medication before treatment, children undergoing desensitizing&#xD;
      treatment in the last 3 months, children with behavioral problems and children with occlusal&#xD;
      problems such as tightening and bruxism.&#xD;
&#xD;
      The instruments of data collection will be a general questionnaire (demographic,&#xD;
      socioeconomic and etiological factors for HMI), clinical examination for diagnosis of HMI,&#xD;
      dental sensitivity test with air syringe and visual analogue scale (to assess the magnitude&#xD;
      of pain). In a clinical file will be recorded the teeth with HMI, the result of the&#xD;
      sensitivity test and magnitude of dental pain before and after treatments. The general&#xD;
      questionnaire will be answered by the parents / guardians. In cases of incomplete&#xD;
      questionnaires, parents / guardians will be contacted by telephone.&#xD;
&#xD;
      The diagnosis of HMI will be performed according to the criteria proposed by the European&#xD;
      Academy of Child Dentistry (WEERHEIJM et al., 2003). The researcher will be calibrated for&#xD;
      the application of the questionnaire and for the diagnosis of HMI lesions.&#xD;
&#xD;
      The study groups will be: treatment with laser therapy (Group 1); treatment with&#xD;
      fluorotherapy (Group 2) and treatment with laser therapy and fluorotherapy (Group 3). For the&#xD;
      treatment of group 1, the low-power, infrared (808nm wavelength) diode laser with a power of&#xD;
      100mW will be used. The mode of irradiation is punctual, in contact and perpendicular to the&#xD;
      dental surface. Three points on the crown of multiradicular teeth (mesial and distal of the&#xD;
      cervical region and central part of the tooth lesion) and two points on the crown of&#xD;
      unirradicular teeth (central point of the cervical region and central part of the tooth&#xD;
      lesion) will be irradiated for 10s per point , 1J per point, with a 72-hour interval between&#xD;
      treatment sessions. The distance between the irradiation points will be about 2 mm. The tip&#xD;
      of the laser equipment will be positioned perpendicular to the application site. The&#xD;
      treatment of Group 2 will be carried out with the application of fluoride varnish, with the&#xD;
      aid of a microbrush. After the application, water will be dripped onto the applied varnish in&#xD;
      order to promote its drying. Fluorotherapy will be performed once a week, totaling 4&#xD;
      sessions. Group 3 will be treated first with the laser (same specifications as Group 1),&#xD;
      followed by application of fluoride varnish (same specifications as Group 2).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 1, 2018</start_date>
  <completion_date type="Actual">December 23, 2018</completion_date>
  <primary_completion_date type="Actual">December 23, 2018</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>
    <intervention_model_description>Groups: treatment with laser therapy (Group 1); treatment with fluorotherapy (Group 2) and treatment with laser therapy and fluorotherapy (Group 3).</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
    <masking_description>The researcher who will evaluate the treatments through the syringe test will be masked as to the type of treatment performed in each patient. The investigator responsible for the treatment and the patient will not be masked.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Dental sensitivity</measure>
    <time_frame>1 month after the onset of treatment</time_frame>
    <description>The dental sensitivity will be evaluated with air from the dental syringe.</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">66</enrollment>
  <condition>Hypomineralization Molar Incisor</condition>
  <arm_group>
    <arm_group_label>Laser therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The low-power, infrared (808nm wavelength) diode laser with a power of 100mW (Therapy EC, DMC) will be used. The mode of irradiation is punctual, in contact and perpendicular to the dental surface. Three points on the crown of multiradicular teeth (mesial and distal of the cervical region and central part of the tooth lesion) and two points on the crown of unirradicular teeth (central point of the cervical region and central part of the tooth lesion) will be irradiated for 10s per point , 1J per point, with a 72-hour interval between treatment sessions. The distance between the irradiation points will be about 2 mm. The tip of the laser equipment will be positioned perpendicular to the application site.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fluorotherapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The treatment will be carried out with the application of fluoride varnish (Duraphat), with the aid of a microbrush. After the application, water will be dripped onto the applied varnish in order to promote its drying. Fluorotherapy will be performed once a week, totaling 4 sessions.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Laser therapy and fluorotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The teeth will be treated first with the laser (same specifications as Laser therapy), followed by application of fluoride varnish (same specifications as Fluorotherapy).</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Laser therapy</intervention_name>
    <description>The low-power, infrared (808nm wavelength) diode laser with a power of 100mW will be used. The mode of irradiation is punctual, in contact and perpendicular to the dental surface. Three points on the crown of multiradicular teeth (mesial and distal of the cervical region and central part of the tooth lesion) and two points on the crown of unirradicular teeth (central point of the cervical region and central part of the tooth lesion) will be irradiated for 10s per point , 1J per point, with a 72-hour interval between treatment sessions. The distance between the irradiation points will be about 2 mm. The tip of the laser equipment will be positioned perpendicular to the application site.</description>
    <arm_group_label>Laser therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Fluorotherapy</intervention_name>
    <description>The treatment will be carried out with the application of fluoride varnish, with the aid of a microbrush. After the application, water will be dripped onto the applied varnish in order to promote its drying. Fluorotherapy will be performed once a week, totaling 4 sessions.</description>
    <arm_group_label>Fluorotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>Laser therapy and Fluorotherapy</intervention_name>
    <description>This group will be treated first with the laser (same specifications as Laser therapy), followed by application of fluoride varnish (same specifications as Fluorotherapy).</description>
    <arm_group_label>Laser therapy and fluorotherapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Children from 8 to 12 years of age;&#xD;
&#xD;
          -  At least one first permanent or incisive erupted incisor (with occlusal / incisal&#xD;
             surface free of gingiva) present in the oral cavity;&#xD;
&#xD;
          -  Teeth presenting hypomineralization lesions sensitive.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Children with enamel malformations linked to syndromes, with dental fluorosis, enamel&#xD;
             hypoplasia or with imperfect amelogenesis;&#xD;
&#xD;
          -  Teeth with loss of dental structure and carious lesion;&#xD;
&#xD;
          -  Children in orthodontic treatment;&#xD;
&#xD;
          -  Children with cognition problems;&#xD;
&#xD;
          -  Children who used any type of analgesic / anti-inflammatory medication before&#xD;
             treatment;&#xD;
&#xD;
          -  Children undergoing desensitizing treatment in the last 3 months&#xD;
&#xD;
          -  Children with behavioral problems;&#xD;
&#xD;
          -  Children with occlusal problems such as tightening and bruxism.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>8 Years</minimum_age>
    <maximum_age>12 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Meire C. Ferreira, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Uniceuma</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Rosyara SC Muniz, DDS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Uniceuma</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Josue Montello, Universidade Ceuma</name>
      <address>
        <city>São Luis</city>
        <state>Maranhão</state>
        <zip>65075-120</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <results_reference>
    <citation>Ghanim A, Silva MJ, Elfrink MEC, Lygidakis NA, Marino RJ, Weerheijm KL, Manton DJ. Molar incisor hypomineralisation (MIH) training manual for clinical field surveys and practice. Eur Arch Paediatr Dent. 2017 Aug;18(4):225-242. doi: 10.1007/s40368-017-0293-9. Epub 2017 Jul 18.</citation>
    <PMID>28721667</PMID>
  </results_reference>
  <results_reference>
    <citation>Lopes AO, Eduardo Cde P, Aranha AC. Clinical evaluation of low-power laser and a desensitizing agent on dentin hypersensitivity. Lasers Med Sci. 2015 Feb;30(2):823-9. doi: 10.1007/s10103-013-1441-z. Epub 2013 Oct 4.</citation>
    <PMID>24197517</PMID>
  </results_reference>
  <results_reference>
    <citation>Aranha AC, Pimenta LA, Marchi GM. Clinical evaluation of desensitizing treatments for cervical dentin hypersensitivity. Braz Oral Res. 2009 Jul-Sep;23(3):333-9. doi: 10.1590/s1806-83242009000300018.</citation>
    <PMID>19893971</PMID>
  </results_reference>
  <results_reference>
    <citation>Lygidakis NA, Wong F, Jalevik B, Vierrou AM, Alaluusua S, Espelid I. Best Clinical Practice Guidance for clinicians dealing with children presenting with Molar-Incisor-Hypomineralisation (MIH): An EAPD Policy Document. Eur Arch Paediatr Dent. 2010 Apr;11(2):75-81. doi: 10.1007/BF03262716.</citation>
    <PMID>20403301</PMID>
  </results_reference>
  <results_reference>
    <citation>Ozgul BM, Saat S, Sonmez H, Oz FT. Clinical evaluation of desensitizing treatment for incisor teeth affected by molar-incisor hypomineralization. J Clin Pediatr Dent. 2013 Winter;38(2):101-5.</citation>
    <PMID>24683770</PMID>
  </results_reference>
  <results_reference>
    <citation>Palazon MT, Scaramucci T, Aranha AC, Prates RA, Lachowski KM, Hanashiro FS, Youssef MN. Immediate and short-term effects of in-office desensitizing treatments for dentinal tubule occlusion. Photomed Laser Surg. 2013 Jun;31(6):274-82. doi: 10.1089/pho.2012.3405. Epub 2013 May 15.</citation>
    <PMID>23675985</PMID>
  </results_reference>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>January 28, 2019</study_first_submitted>
  <study_first_submitted_qc>January 28, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 30, 2019</study_first_posted>
  <last_update_submitted>November 21, 2019</last_update_submitted>
  <last_update_submitted_qc>November 21, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 25, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Universidade Ceuma</investigator_affiliation>
    <investigator_full_name>Meire Coelho Ferreira</investigator_full_name>
    <investigator_title>Study Director</investigator_title>
  </responsible_party>
  <keyword>hypomineralization molar incisor</keyword>
  <keyword>Child</keyword>
  <keyword>Laser Therapy</keyword>
  <keyword>Tooth Sensitivity</keyword>
  <!-- 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/NCT03823170
org study id: MCCF-230784-RM
nct id: NCT03823170
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
To investigate the efficacy of laser therapy associated with fluorotherapy in the
      desensibitization of hypomineralized teeth in children 8 to 12 years of age. A randomized
      blinded clinical trial will be conducted. The instruments used will be a questionnaire
      general, clinical examination, dental air syringe (evaluation of dental sensitivity) and
      visual analogue scale (evaluation of the magnitude of dental sensitivity). Teeth with
      hypomineralization molar-incisor (HMI) and the results of sensitivity and magnitude of dental
      pain before and after the treatments will be recorded in a clinical record. The study groups
      will be: treatment with laser therapy (Group 1); treatment with fluorotherapy (Group 2) and
      treatment with laser therapy and fluorotherapy (Group 3).
A blinded randomized clinical trial will be conducted. The study will be conducted with
      children attending the Pediatric Dentistry Clinic of the Florence Institute's undergraduate
      course, in São Luís, Maranhão, Brazil. As inclusion criteria, children from 8 to 12 years of
      age will be adopted, with at least one first permanent or incisive erupted incisor (with
      occlusal / incisal surface free of gingiva) present in the oral cavity and presenting
      sensitive hypomineralization lesions. Exclusion criteria will be children with enamel
      malformations linked to syndromes, with dental fluorosis, enamel hypoplasia or with imperfect
      amelogenesis, teeth with loss of structure dental and carious lesions, children in
      orthodontic treatment, children with cognition problems, children who used any type of
      analgesic / anti-inflammatory medication before treatment, children undergoing desensitizing
      treatment in the last 3 months, children with behavioral problems and children with occlusal
      problems such as tightening and bruxism.

      The instruments of data collection will be a general questionnaire (demographic,
      socioeconomic and etiological factors for HMI), clinical examination for diagnosis of HMI,
      dental sensitivity test with air syringe and visual analogue scale (to assess the magnitude
      of pain). In a clinical file will be recorded the teeth with HMI, the result of the
      sensitivity test and magnitude of dental pain before and after treatments. The general
      questionnaire will be answered by the parents / guardians. In cases of incomplete
      questionnaires, parents / guardians will be contacted by telephone.

      The diagnosis of HMI will be performed according to the criteria proposed by the European
      Academy of Child Dentistry (WEERHEIJM et al., 2003). The researcher will be calibrated for
      the application of the questionnaire and for the diagnosis of HMI lesions.

      The study groups will be: treatment with laser therapy (Group 1); treatment with
      fluorotherapy (Group 2) and treatment with laser therapy and fluorotherapy (Group 3). For the
      treatment of group 1, the low-power, infrared (808nm wavelength) diode laser with a power of
      100mW will be used. The mode of irradiation is punctual, in contact and perpendicular to the
      dental surface. Three points on the crown of multiradicular teeth (mesial and distal of the
      cervical region and central part of the tooth lesion) and two points on the crown of
      unirradicular teeth (central point of the cervical region and central part of the tooth
      lesion) will be irradiated for 10s per point , 1J per point, with a 72-hour interval between
      treatment sessions. The distance between the irradiation points will be about 2 mm. The tip
      of the laser equipment will be positioned perpendicular to the application site. The
      treatment of Group 2 will be carried out with the application of fluoride varnish, with the
      aid of a microbrush. After the application, water will be dripped onto the applied varnish in
      order to promote its drying. Fluorotherapy will be performed once a week, totaling 4
      sessions. Group 3 will be treated first with the laser (same specifications as Group 1),
      followed by application of fluoride varnish (same specifications as Group 2).
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Groups: treatment with laser therapy (Group 1); treatment with fluorotherapy (Group 2) and treatment with laser therapy and fluorotherapy (Group 3).
primary purpose: Treatment
masking: Single (Outcomes Assessor)
masking description: The researcher who will evaluate the treatments through the syringe test will be masked as to the type of treatment performed in each patient. The investigator responsible for the treatment and the patient will not be masked.
measure: Dental sensitivity
time frame: 1 month after the onset of treatment
description: The dental sensitivity will be evaluated with air from the dental syringe.
arm group label: Laser therapy
arm group type: Experimental
description: The low-power, infrared (808nm wavelength) diode laser with a power of 100mW (Therapy EC, DMC) will be used. The mode of irradiation is punctual, in contact and perpendicular to the dental surface. Three points on the crown of multiradicular teeth (mesial and distal of the cervical region and central part of the tooth lesion) and two points on the crown of unirradicular teeth (central point of the cervical region and central part of the tooth lesion) will be irradiated for 10s per point , 1J per point, with a 72-hour interval between treatment sessions. The distance between the irradiation points will be about 2 mm. The tip of the laser equipment will be positioned perpendicular to the application site.
arm group label: Fluorotherapy
arm group type: Active Comparator
description: The treatment will be carried out with the application of fluoride varnish (Duraphat), with the aid of a microbrush. After the application, water will be dripped onto the applied varnish in order to promote its drying. Fluorotherapy will be performed once a week, totaling 4 sessions.
arm group label: Laser therapy and fluorotherapy
arm group type: Experimental
description: The teeth will be treated first with the laser (same specifications as Laser therapy), followed by application of fluoride varnish (same specifications as Fluorotherapy).
intervention type: Radiation
intervention name: Laser therapy
description: The low-power, infrared (808nm wavelength) diode laser with a power of 100mW will be used. The mode of irradiation is punctual, in contact and perpendicular to the dental surface. Three points on the crown of multiradicular teeth (mesial and distal of the cervical region and central part of the tooth lesion) and two points on the crown of unirradicular teeth (central point of the cervical region and central part of the tooth lesion) will be irradiated for 10s per point , 1J per point, with a 72-hour interval between treatment sessions. The distance between the irradiation points will be about 2 mm. The tip of the laser equipment will be positioned perpendicular to the application site.
arm group label: Laser therapy
intervention type: Procedure
intervention name: Fluorotherapy
description: The treatment will be carried out with the application of fluoride varnish, with the aid of a microbrush. After the application, water will be dripped onto the applied varnish in order to promote its drying. Fluorotherapy will be performed once a week, totaling 4 sessions.
arm group label: Fluorotherapy
intervention type: Combination Product
intervention name: Laser therapy and Fluorotherapy
description: This group will be treated first with the laser (same specifications as Laser therapy), followed by application of fluoride varnish (same specifications as Fluorotherapy).
arm group label: Laser therapy and fluorotherapy
criteria: 
gender: All
minimum age: 8 Years
maximum age: 12 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Meire C. Ferreira, PhD
role: Study Director
affiliation: Uniceuma
last name: Rosyara SC Muniz, DDS
role: Principal Investigator
affiliation: Uniceuma
facility: 
country: Brazil
citation: Ghanim A, Silva MJ, Elfrink MEC, Lygidakis NA, Marino RJ, Weerheijm KL, Manton DJ. Molar incisor hypomineralisation (MIH) training manual for clinical field surveys and practice. Eur Arch Paediatr Dent. 2017 Aug;18(4):225-242. doi: 10.1007/s40368-017-0293-9. Epub 2017 Jul 18.
PMID: 28721667
citation: Lopes AO, Eduardo Cde P, Aranha AC. Clinical evaluation of low-power laser and a desensitizing agent on dentin hypersensitivity. Lasers Med Sci. 2015 Feb;30(2):823-9. doi: 10.1007/s10103-013-1441-z. Epub 2013 Oct 4.
PMID: 24197517
citation: Aranha AC, Pimenta LA, Marchi GM. Clinical evaluation of desensitizing treatments for cervical dentin hypersensitivity. Braz Oral Res. 2009 Jul-Sep;23(3):333-9. doi: 10.1590/s1806-83242009000300018.
PMID: 19893971
citation: Lygidakis NA, Wong F, Jalevik B, Vierrou AM, Alaluusua S, Espelid I. Best Clinical Practice Guidance for clinicians dealing with children presenting with Molar-Incisor-Hypomineralisation (MIH): An EAPD Policy Document. Eur Arch Paediatr Dent. 2010 Apr;11(2):75-81. doi: 10.1007/BF03262716.
PMID: 20403301
citation: Ozgul BM, Saat S, Sonmez H, Oz FT. Clinical evaluation of desensitizing treatment for incisor teeth affected by molar-incisor hypomineralization. J Clin Pediatr Dent. 2013 Winter;38(2):101-5.
PMID: 24683770
citation: Palazon MT, Scaramucci T, Aranha AC, Prates RA, Lachowski KM, Hanashiro FS, Youssef MN. Immediate and short-term effects of in-office desensitizing treatments for dentinal tubule occlusion. Photomed Laser Surg. 2013 Jun;31(6):274-82. doi: 10.1089/pho.2012.3405. Epub 2013 May 15.
PMID: 23675985
responsible party type: Principal Investigator
investigator affiliation: Universidade Ceuma
investigator full name: Meire Coelho Ferreira
investigator title: Study Director