<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/NCT02240563</url>
  </required_header>
  <id_info>
    <org_study_id>CAPPesq 11459</org_study_id>
    <nct_id>NCT02240563</nct_id>
  </id_info>
  <brief_title>Low Level Laser Therapy for Autoimmune Thyroiditis</brief_title>
  <official_title>Long-term Follow-up After Treatment of Chronic Autoimmune Thyroiditis With Low Level Laser</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Sao Paulo General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Fundação de Amparo à Pesquisa do Estado de São Paulo</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Sao Paulo General Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      INTRODUCTION: Chronic autoimmune thyroiditis (TCA) is the main cause of acquired&#xD;
      hypothyroidism, which requires continuous treatment with levothyroxine (LT4). A randomized,&#xD;
      placebo-controlled trial including 43 patients with hypothyroidism caused by TCA without&#xD;
      nodules on ultrasonography study (US) was conducted from March 2006 to March 2009&#xD;
      (NCT01129492). Among them, 23 were submitted to low-level laser therapy (LLLT) and 20 to&#xD;
      placebo. The LLLT was effective in improving the echogenicity, the volume and of the thyroid&#xD;
      vascularization pattern by US. There was also improvement in the thyroid function and&#xD;
      reduction of serum thyroid peroxidase antibodies (TPOAb). Although the results have shown&#xD;
      promising and LLLT has shown to be safe in many study models, the long-term LLLT actions on&#xD;
      the thyroid parenchyma are unknown. Thus, the objective of this study is to perform&#xD;
      biochemical tests and thyroid US six years after the clinical trial interventions to evaluate&#xD;
      levothyroxine dose, serum levels of autoantibodies and, especially, the frequency and nature&#xD;
      of nodules in the gland and then compare these variables between LLLT and placebo groups.&#xD;
      METHODS: This study will include the trial participants performed six years before. The&#xD;
      levothyroxine dose and serum levels of thyrotropin (TSH), T3, T4, free T4, TPOAb and&#xD;
      anti-thyroglobulin antibodies (TgAb) will be evaluated in these patients. The thyroid US will&#xD;
      assess the texture (with particular attention to identifying nodules), echogenicity, volume,&#xD;
      as well as vascularization of the gland. The US nodules features, such as dimensions, shape,&#xD;
      margins, extracapsular invasion, echogenicity, texture, hypoechoic halo, calcification,&#xD;
      internal content, vascularization pattern and resistivity index will be searched. Regional&#xD;
      lymph nodes and other characteristics will be also investigated. The USs will be carried out&#xD;
      by only one examiner who will be blinded for the previously performed intervention (LILT or&#xD;
      placebo). The same investigator will execute a fine needle aspiration (FNA) of patients with&#xD;
      thyroid nodules. The cytological analysis of the material collected from the nodules will be&#xD;
      undertaken by a pathologist who will be also blinded for the treatment assignments. RESULTS:&#xD;
      The following variables will be compared between the two groups: levothyroxine doses,&#xD;
      antithyroid antibodies, US parameters, thyroid nodules (if detected) and in this case, the&#xD;
      result of their respective FNA.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">March 2016</completion_date>
  <primary_completion_date type="Actual">March 2016</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants with Thyroid Nodules as a Measure of Safety</measure>
    <time_frame>Six Years after Each Patient Treatment</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Serum Levels of Anti-Thyroglobulin Antibodies as a Measure of Long Term Efficacy</measure>
    <time_frame>Six Years after Each Patient Treatment</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>The Levothyroxine Required Dose as a Measure of Long-Term Efficacy</measure>
    <time_frame>Six Years after Each Patient Treatment</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">43</enrollment>
  <condition>Autoimmune Thyroiditis</condition>
  <arm_group>
    <arm_group_label>Low-level laser therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This group of patients was treated with a continuous wave diode laser device (830 nanometer, infrared) with a beam area of 0.002827 cm2 using the punctual method on the continuous emission mode at an output power of 50 milliwatts and a fluence of 707 Joules/cm2 six years before.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Non laser ordinary red light</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>This group of patients was treated using the same method and equipment, except that a non laser ordinary red light, an output power of 0.1 Watt and a fluence of 1.41 Joules/cm2 and an irradiance value of 0.0002827 Watts/cm2 (the placebo), indistinguishable from the laser beam, was used. Therefore, the patients were blinded to which treatment they received.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Low-level laser therapy</intervention_name>
    <arm_group_label>Low-level laser therapy</arm_group_label>
    <other_name>Low-power laser therapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Non laser ordinary red light</intervention_name>
    <arm_group_label>Non laser ordinary red light</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        All patients who have hypothyroidism caused by autoimmune thyroiditis included in the&#xD;
        randomized, placebo controlled clinical trial (NCT01129492)&#xD;
&#xD;
        -&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        All patients who have hypothyroidism caused by autoimmune thyroiditis included in the&#xD;
        aforementioned trial (NCT01129492) who underwent surgery and/or therapeutic administration&#xD;
        of radioiodine for thyroid diseases during the period between the initial assessment of&#xD;
        patients up to the present study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Maria Cristina Chammas, MD</last_name>
    <role>Study Director</role>
    <affiliation>University of Sao Paulo General Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Carlos Alberto Buchpiguel, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>University of Sao Paulo General Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Danilo B Höfling, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Sao Paulo General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Sao Paulo General Hospital, Radiology Institute</name>
      <address>
        <city>Sao Paulo</city>
        <zip>05403-000</zip>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Sao Paulo General Hospital</name>
      <address>
        <city>São Paulo</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Brazil</country>
  </location_countries>
  <reference>
    <citation>Hofling DB, Chavantes MC, Juliano AG, Cerri GG, Knobel M, Yoshimura EM, Chammas MC. Low-level laser in the treatment of patients with hypothyroidism induced by chronic autoimmune thyroiditis: a randomized, placebo-controlled clinical trial. Lasers Med Sci. 2013 May;28(3):743-53. doi: 10.1007/s10103-012-1129-9. Epub 2012 Jun 21.</citation>
    <PMID>22718472</PMID>
  </reference>
  <reference>
    <citation>Hofling DB, Chavantes MC, Juliano AG, Cerri GG, Romao R, Yoshimura EM, Chammas MC. Low-level laser therapy in chronic autoimmune thyroiditis: a pilot study. Lasers Surg Med. 2010 Aug;42(6):589-96. doi: 10.1002/lsm.20941.</citation>
    <PMID>20662037</PMID>
  </reference>
  <reference>
    <citation>Hofling DB, Chavantes MC, Juliano AG, Cerri GG, Knobel M, Yoshimura EM, Chammas MC. Assessment of the effects of low-level laser therapy on the thyroid vascularization of patients with autoimmune hypothyroidism by color Doppler ultrasound. ISRN Endocrinol. 2012;2012:126720. doi: 10.5402/2012/126720. Epub 2012 Dec 17.</citation>
    <PMID>23316383</PMID>
  </reference>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>June 23, 2014</study_first_submitted>
  <study_first_submitted_qc>September 11, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 15, 2014</study_first_posted>
  <last_update_submitted>May 2, 2017</last_update_submitted>
  <last_update_submitted_qc>May 2, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 5, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Sao Paulo General Hospital</investigator_affiliation>
    <investigator_full_name>Danilo Bianchini Hofling</investigator_full_name>
    <investigator_title>MD, University of Sao Paulo General Hospital</investigator_title>
  </responsible_party>
  <keyword>autoimmune thyroiditis</keyword>
  <keyword>LLLT</keyword>
  <keyword>safety</keyword>
  <keyword>ultrasound</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thyroiditis</mesh_term>
    <mesh_term>Thyroiditis, Autoimmune</mesh_term>
    <mesh_term>Hashimoto Disease</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/NCT02240563
org study id: CAPPesq 11459
nct id: NCT02240563
lead sponsor: 
collaborator: 
has dmc: No
INTRODUCTION: Chronic autoimmune thyroiditis (TCA) is the main cause of acquired
      hypothyroidism, which requires continuous treatment with levothyroxine (LT4). A randomized,
      placebo-controlled trial including 43 patients with hypothyroidism caused by TCA without
      nodules on ultrasonography study (US) was conducted from March 2006 to March 2009
      (NCT01129492). Among them, 23 were submitted to low-level laser therapy (LLLT) and 20 to
      placebo. The LLLT was effective in improving the echogenicity, the volume and of the thyroid
      vascularization pattern by US. There was also improvement in the thyroid function and
      reduction of serum thyroid peroxidase antibodies (TPOAb). Although the results have shown
      promising and LLLT has shown to be safe in many study models, the long-term LLLT actions on
      the thyroid parenchyma are unknown. Thus, the objective of this study is to perform
      biochemical tests and thyroid US six years after the clinical trial interventions to evaluate
      levothyroxine dose, serum levels of autoantibodies and, especially, the frequency and nature
      of nodules in the gland and then compare these variables between LLLT and placebo groups.
      METHODS: This study will include the trial participants performed six years before. The
      levothyroxine dose and serum levels of thyrotropin (TSH), T3, T4, free T4, TPOAb and
      anti-thyroglobulin antibodies (TgAb) will be evaluated in these patients. The thyroid US will
      assess the texture (with particular attention to identifying nodules), echogenicity, volume,
      as well as vascularization of the gland. The US nodules features, such as dimensions, shape,
      margins, extracapsular invasion, echogenicity, texture, hypoechoic halo, calcification,
      internal content, vascularization pattern and resistivity index will be searched. Regional
      lymph nodes and other characteristics will be also investigated. The USs will be carried out
      by only one examiner who will be blinded for the previously performed intervention (LILT or
      placebo). The same investigator will execute a fine needle aspiration (FNA) of patients with
      thyroid nodules. The cytological analysis of the material collected from the nodules will be
      undertaken by a pathologist who will be also blinded for the treatment assignments. RESULTS:
      The following variables will be compared between the two groups: levothyroxine doses,
      antithyroid antibodies, US parameters, thyroid nodules (if detected) and in this case, the
      result of their respective FNA.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of Participants with Thyroid Nodules as a Measure of Safety
time frame: Six Years after Each Patient Treatment
measure: Serum Levels of Anti-Thyroglobulin Antibodies as a Measure of Long Term Efficacy
time frame: Six Years after Each Patient Treatment
measure: The Levothyroxine Required Dose as a Measure of Long-Term Efficacy
time frame: Six Years after Each Patient Treatment
arm group label: Low-level laser therapy
arm group type: Experimental
description: This group of patients was treated with a continuous wave diode laser device (830 nanometer, infrared) with a beam area of 0.002827 cm2 using the punctual method on the continuous emission mode at an output power of 50 milliwatts and a fluence of 707 Joules/cm2 six years before.
arm group label: Non laser ordinary red light
arm group type: Placebo Comparator
description: This group of patients was treated using the same method and equipment, except that a non laser ordinary red light, an output power of 0.1 Watt and a fluence of 1.41 Joules/cm2 and an irradiance value of 0.0002827 Watts/cm2 (the placebo), indistinguishable from the laser beam, was used. Therefore, the patients were blinded to which treatment they received.
intervention type: Procedure
intervention name: Low-level laser therapy
arm group label: Low-level laser therapy
other name: Low-power laser therapy
intervention type: Procedure
intervention name: Non laser ordinary red light
arm group label: Non laser ordinary red light
other name: Placebo
criteria: 
gender: All
minimum age: 20 Years
maximum age: 60 Years
healthy volunteers: No
last name: Maria Cristina Chammas, MD
role: Study Director
affiliation: University of Sao Paulo General Hospital
last name: Carlos Alberto Buchpiguel, PhD
role: Study Chair
affiliation: University of Sao Paulo General Hospital
last name: Danilo B Höfling, MD
role: Principal Investigator
affiliation: University of Sao Paulo General Hospital
facility: 
facility: 
country: Brazil
citation: Hofling DB, Chavantes MC, Juliano AG, Cerri GG, Knobel M, Yoshimura EM, Chammas MC. Low-level laser in the treatment of patients with hypothyroidism induced by chronic autoimmune thyroiditis: a randomized, placebo-controlled clinical trial. Lasers Med Sci. 2013 May;28(3):743-53. doi: 10.1007/s10103-012-1129-9. Epub 2012 Jun 21.
PMID: 22718472
citation: Hofling DB, Chavantes MC, Juliano AG, Cerri GG, Romao R, Yoshimura EM, Chammas MC. Low-level laser therapy in chronic autoimmune thyroiditis: a pilot study. Lasers Surg Med. 2010 Aug;42(6):589-96. doi: 10.1002/lsm.20941.
PMID: 20662037
citation: Hofling DB, Chavantes MC, Juliano AG, Cerri GG, Knobel M, Yoshimura EM, Chammas MC. Assessment of the effects of low-level laser therapy on the thyroid vascularization of patients with autoimmune hypothyroidism by color Doppler ultrasound. ISRN Endocrinol. 2012;2012:126720. doi: 10.5402/2012/126720. Epub 2012 Dec 17.
PMID: 23316383
responsible party type: Principal Investigator
investigator affiliation: University of Sao Paulo General Hospital
investigator full name: Danilo Bianchini Hofling
investigator title: MD, University of Sao Paulo General Hospital
mesh term: Thyroiditis
mesh term: Thyroiditis, Autoimmune
mesh term: Hashimoto Disease