xml: <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/NCT05989555</url>
    </required_header>
    <id_info>
      <org_study_id>2023-16623</org_study_id>
      <nct_id>NCT05989555</nct_id>
    </id_info>
    <brief_title>Effects of Radioactive Iodine on the Immune System in Thyroid Cancer</brief_title>
    <acronym>SCIMITAR</acronym>
    <official_title>Effects on the Systemic Innate Immune System by Radioactive Iodine Treatment in Non-medullary Thyroid Cancer Patients</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Radboud University Medical Center</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Radboud University Medical Center</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>
        Blood will be drawn 1 month before and 2 month after regular radioactive iodine treatment.&#xD;
        Monocytes will be isolated. The three main outcomes are whole blood counts, cytokine&#xD;
        production upon in vitro stimulation of monocytes and in vitro ROS production by monocytes.&#xD;
        These results are compared between patients treated in adjuvant setting and patients treated&#xD;
        for persistent structural disease, and between pre- and post-treatment status.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Earlier studies have shown that, particularly advanced, thyroid carcinomas are highly&#xD;
        immunogenic tumors. The immune system is involved in both pathogenesis and progression of&#xD;
        thyroid carcinoma (TC), as in other malignancies. For example, it is known that increased&#xD;
        tumor infiltration with tumor-associated macrophages is associated with decreased survival in&#xD;
        TC patients. In a previous study from our group, changes in the programming of myeloid immune&#xD;
        cells were identified in newly diagnoses TC patients. That study showed that upon&#xD;
        stimulation, cytokine production was decreased in monocytes from TC patients when compared to&#xD;
        monocytes from healthy volunteers or from patients with benign thyroid tumors. Also, reactive&#xD;
        oxygen species (ROS) production (known to be tumorigenic) from monocytes was increased in TC&#xD;
        patients when compared to healthy volunteers. In the mentioned study, several effects of&#xD;
        radioactive iodine (RAI)-treatment, after surgery, on the systemic immune system were&#xD;
        observed. For instance, lymphocyte counts were significantly reduced after treatment with&#xD;
        RAI, an effect also observed in other studies. Moreover, after RAI-treatment, ROS levels&#xD;
        produced by monocytes decreased to levels similar to those produced by monocytes of healthy&#xD;
        controls. Although, the effect of RAI-treatment on ROS-production was less pronounced than&#xD;
        that of surgery. There was no clear effect of RAI-treatment on the cytokine production&#xD;
        capacity. However, it should be noted that in most patients in this study RAI was&#xD;
        administered in a setting of remnant ablation, meaning that only a low dose of RAI was&#xD;
        administered and that only a very low amount (or none) of cancer cells were present at the&#xD;
        time of administration. Furthermore, the number of included patients was too low to perform&#xD;
        subgroup analyses. The current study aims to assess the effect of RAI-treatment in patients&#xD;
        with structural disease, as a higher dose of beta-radiation will be present in these&#xD;
        patients, and compare these effects to that in patients treated with RAI in an adjuvant&#xD;
        setting.&#xD;
  &#xD;
        The investigators hypothesize that RAI-treatment will have a more pronounced effect on the&#xD;
        systemic innate immune system in patients with structural disease when compared to patients&#xD;
        treated in an adjuvant setting. This study will give us more insights in the interplay&#xD;
        between RAI and the immune system in patients with TC.&#xD;
  &#xD;
        The aim of the study is to assess the effect of RAI-treatment on the innate immune system in&#xD;
        TC patients and to compare these effects between patients with and without structural disease&#xD;
        in a prospective explorative study.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 1, 2023</start_date>
    <completion_date type="Anticipated">December 1, 2025</completion_date>
    <primary_completion_date type="Anticipated">June 1, 2025</primary_completion_date>
    <study_type>Observational</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <observational_model>Cohort</observational_model>
      <time_perspective>Prospective</time_perspective>
    </study_design_info>
    <primary_outcome>
      <measure>Whole blood counts</measure>
      <time_frame>2 months</time_frame>
      <description>Whole blood counts with leukocyte subtypes (neutrophils, lymphocytes and monocytes) are compared before and after radioactive iodine treatment</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Cytokine production upon monocyte stimulation</measure>
      <time_frame>2 months</time_frame>
      <description>Cytokine produciton (tumor necrosis factor, interleukin-6, interleukin-8) will be compared before and after treatment with radioactive iodine</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Reactive oxygen species (ROS) production by monocytes</measure>
      <time_frame>2 months</time_frame>
      <description>In vitro ROS production by monocytes will be compared before and after treatment with radioactive iodine</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Monocyte transcriptome</measure>
      <time_frame>2 months</time_frame>
      <description>Possibly, transcriptome of monocytes will be compared before and after treatment with radioactive iodine</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Plasma proteome</measure>
      <time_frame>2 months</time_frame>
      <description>Possibly, plasma proteome (especially inflammatory markers) will be compared before and treatment with radioactive iodine.</description>
    </secondary_outcome>
    <number_of_groups>2</number_of_groups>
    <enrollment type="Anticipated">30</enrollment>
    <condition>Thyroid Carcinoma, Nonmedullary</condition>
    <arm_group>
      <arm_group_label>I/adjuvant</arm_group_label>
      <description>15 patients with thyroid carcinoma that are treated with radioacitive iodine in an adjuvant setting</description>
    </arm_group>
    <arm_group>
      <arm_group_label>II/structutral disease</arm_group_label>
      <description>15 patients with thyroid carcinoma that are treated with radioactive iodine with the indication of persistent structural disease</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Blood drawing</intervention_name>
      <description>Blood is drawn twice in all subjects. Once before treatment with radioacitve iodine and once after.</description>
      <arm_group_label>I/adjuvant</arm_group_label>
      <arm_group_label>II/structutral disease</arm_group_label>
    </intervention>
    <biospec_retention>Samples Without DNA</biospec_retention>
    <biospec_descr>
      <textblock>
        Peripheral blood mononuclear cells and monocytes will be isolated from whole blood.&#xD;
  &#xD;
        The monocytes will be stimulated in vitro. Supernatants will be stored.&#xD;
      </textblock>
    </biospec_descr>
    <eligibility>
      <study_pop>
        <textblock>
          Thirty patients with non-medulary thyroid carcinoma&#xD;
        </textblock>
      </study_pop>
      <sampling_method>Non-Probability Sample</sampling_method>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Pathologically confirmed non-medullary thyroid cancer&#xD;
  &#xD;
            -  Undergoing radioactive iodine treatment in an adjuvant setting or for persistent&#xD;
               structural disease&#xD;
  &#xD;
            -  Aged ≥ 18 years&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Inflammatory or infectious comorbidities&#xD;
  &#xD;
            -  Using medication interfering with the immune system&#xD;
  &#xD;
            -  Pregnancy&#xD;
  &#xD;
            -  A self-reported alcohol consumption of &gt;21 units per week&#xD;
  &#xD;
            -  Other active malignancies, defined as malignancies not in complete remission for &lt;2&#xD;
               years&#xD;
  &#xD;
            -  Previous systemic anti-cancer treatment such as chemotherapy, targeted therapy,&#xD;
               radiotherapy or immunotherapy within 3 years before study procedures&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Pepijn van Houten, M.D.</last_name>
      <phone>+31243614599</phone>
      <email>pepijn.vanhouten@radboudumc.nl</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Prashant Changoer, Msc.</last_name>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Radboud University Medical Center</name>
        <address>
          <city>Nijmegen</city>
          <country>Netherlands</country>
        </address>
      </facility>
      <contact>
        <last_name>Pepijn van Houten, Msc.</last_name>
        <phone>+31-24-3614599</phone>
        <email>pepijn.vanhouten@radboudumc.nl</email>
      </contact>
    </location>
    <location_countries>
      <country>Netherlands</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 4, 2023</study_first_submitted>
    <study_first_submitted_qc>August 4, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 13, 2023</last_update_submitted>
    <last_update_submitted_qc>August 13, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 15, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>radioactive iodine</keyword>
    <keyword>innate immune system</keyword>
    <keyword>monocytes</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Thyroid Neoplasms</mesh_term>
      <mesh_term>Thyroid Cancer, Papillary</mesh_term>
      <mesh_term>Thyroid Diseases</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05989555
  org study id: 2023-16623
  nct id: NCT05989555
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  Blood will be drawn 1 month before and 2 month after regular radioactive iodine treatment.
        Monocytes will be isolated. The three main outcomes are whole blood counts, cytokine
        production upon in vitro stimulation of monocytes and in vitro ROS production by monocytes.
        These results are compared between patients treated in adjuvant setting and patients treated
        for persistent structural disease, and between pre- and post-treatment status.
  Earlier studies have shown that, particularly advanced, thyroid carcinomas are highly
        immunogenic tumors. The immune system is involved in both pathogenesis and progression of
        thyroid carcinoma (TC), as in other malignancies. For example, it is known that increased
        tumor infiltration with tumor-associated macrophages is associated with decreased survival in
        TC patients. In a previous study from our group, changes in the programming of myeloid immune
        cells were identified in newly diagnoses TC patients. That study showed that upon
        stimulation, cytokine production was decreased in monocytes from TC patients when compared to
        monocytes from healthy volunteers or from patients with benign thyroid tumors. Also, reactive
        oxygen species (ROS) production (known to be tumorigenic) from monocytes was increased in TC
        patients when compared to healthy volunteers. In the mentioned study, several effects of
        radioactive iodine (RAI)-treatment, after surgery, on the systemic immune system were
        observed. For instance, lymphocyte counts were significantly reduced after treatment with
        RAI, an effect also observed in other studies. Moreover, after RAI-treatment, ROS levels
        produced by monocytes decreased to levels similar to those produced by monocytes of healthy
        controls. Although, the effect of RAI-treatment on ROS-production was less pronounced than
        that of surgery. There was no clear effect of RAI-treatment on the cytokine production
        capacity. However, it should be noted that in most patients in this study RAI was
        administered in a setting of remnant ablation, meaning that only a low dose of RAI was
        administered and that only a very low amount (or none) of cancer cells were present at the
        time of administration. Furthermore, the number of included patients was too low to perform
        subgroup analyses. The current study aims to assess the effect of RAI-treatment in patients
        with structural disease, as a higher dose of beta-radiation will be present in these
        patients, and compare these effects to that in patients treated with RAI in an adjuvant
        setting.
  
        The investigators hypothesize that RAI-treatment will have a more pronounced effect on the
        systemic innate immune system in patients with structural disease when compared to patients
        treated in an adjuvant setting. This study will give us more insights in the interplay
        between RAI and the immune system in patients with TC.
  
        The aim of the study is to assess the effect of RAI-treatment on the innate immune system in
        TC patients and to compare these effects between patients with and without structural disease
        in a prospective explorative study.
  observational model: Cohort
  time perspective: Prospective
  measure: Whole blood counts
  time frame: 2 months
  description: Whole blood counts with leukocyte subtypes (neutrophils, lymphocytes and monocytes) are compared before and after radioactive iodine treatment
  measure: Cytokine production upon monocyte stimulation
  time frame: 2 months
  description: Cytokine produciton (tumor necrosis factor, interleukin-6, interleukin-8) will be compared before and after treatment with radioactive iodine
  measure: Reactive oxygen species (ROS) production by monocytes
  time frame: 2 months
  description: In vitro ROS production by monocytes will be compared before and after treatment with radioactive iodine
  measure: Monocyte transcriptome
  time frame: 2 months
  description: Possibly, transcriptome of monocytes will be compared before and after treatment with radioactive iodine
  measure: Plasma proteome
  time frame: 2 months
  description: Possibly, plasma proteome (especially inflammatory markers) will be compared before and treatment with radioactive iodine.
  arm group label: I/adjuvant
  description: 15 patients with thyroid carcinoma that are treated with radioacitive iodine in an adjuvant setting
  arm group label: II/structutral disease
  description: 15 patients with thyroid carcinoma that are treated with radioactive iodine with the indication of persistent structural disease
  intervention type: Other
  intervention name: Blood drawing
  description: Blood is drawn twice in all subjects. Once before treatment with radioacitve iodine and once after.
  arm group label: I/adjuvant
  arm group label: II/structutral disease
  Peripheral blood mononuclear cells and monocytes will be isolated from whole blood.
  
        The monocytes will be stimulated in vitro. Supernatants will be stored.
  study pop: 
  sampling method: Non-Probability Sample
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Pepijn van Houten, M.D.
  phone: +31243614599
  email: pepijn.vanhouten@radboudumc.nl
  last name: Prashant Changoer, Msc.
  facility: 
  contact: 
  country: Netherlands
  responsible party type: Sponsor
  mesh term: Thyroid Neoplasms
  mesh term: Thyroid Cancer, Papillary
  mesh term: Thyroid Diseases
  sharing ipd: Undecided