<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/NCT03012438</url>
  </required_header>
  <id_info>
    <org_study_id>NL57409.068.16</org_study_id>
    <nct_id>NCT03012438</nct_id>
  </id_info>
  <brief_title>NIRF for Parathyroid Visualization: a Pilot Study</brief_title>
  <official_title>The Use of Near-Infrared Fluorescence Imaging in Parathyroid Visualization During Thyroid Surgery: a Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Maastricht University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Maastricht University Medical Center</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>
      During surgery in which the thyroid is removed (thyroidectomy), the identification of&#xD;
      parathyroid glands, that should be saved, can be challenging. Therefore, there is need for&#xD;
      accurate intraoperative guidance. Earlier animal studies show that the parathyroid glands can&#xD;
      be identified by the use of the Near Infrared Fluorescent dye Indocyanine green (ICG).&#xD;
&#xD;
      Our hypothesis is therefore, that the use of ICG-based fluorescence imaging during thyroid&#xD;
      surgery will provide real-time intraoperative visualization of the parathyroid glands.&#xD;
&#xD;
      This prospective observational feasibility study aims to evaluate the feasibility of the use&#xD;
      of ICG in identifying the parathyroid glands during thyroid surgery. 30 patients (age &gt;18&#xD;
      years) who are already regularly scheduled for thyroid surgery; i.e. patients undergoing&#xD;
      total thyroidectomy are suitable for inclusion. In all patients, undergoing total&#xD;
      thyroidectomy infrared fluorescence imaging, using a per-operative intravenous injection of&#xD;
      7.5 mg ICG, will be tested on feasibility and imaging characteristics.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this study, the feasibility of the use of NIR fluorescence imaging for the identification&#xD;
      of the parathyroid glands during thyroid surgery will be explored.&#xD;
&#xD;
      Per-operatively: The surgery will start as usual. When the surgeon would normally search for&#xD;
      the parathyroid glands, 7.5 mg of ICG will be administered intravenously through the infusion&#xD;
      in the patients arm. An intravenous administration is chosen because of the minimal invasive&#xD;
      nature and results of the described earlier case series in which ICG was also administered&#xD;
      via peripheral infusion. Directly after that, the fluorescence system can be switched to&#xD;
      fluorescence mode. The surgeon will determine whether the parathyroid glands are visible now.&#xD;
      If needed, due to washout, a second dose of 7.5 mg of ICG can be administered. After&#xD;
      identification of the parathyroid glands, surgery will continue as in the standard situation,&#xD;
      until there is a desire to visualize the parathyroid glands again, then another dose of ICG&#xD;
      can be given. Time until first identification of the parathyroid glands and total surgical&#xD;
      time will be measured. After complete removal of the thyroid, another 7.5 mg of ICG will be&#xD;
      administered intravenously to visualize the vascularization of the parathyroid gland. The&#xD;
      intensity will be subjectively scored: 1 parathyroid black after injection of ICG, 2&#xD;
      partially vascularized, or 3 parathyroid is green; well vascularized. The fluorescence system&#xD;
      will be used to record the whole procedure. Directly after the procedure the researcher will&#xD;
      ask the surgeon whether he or she thinks the technique is feasible.&#xD;
&#xD;
      Postoperatively: As in standard care, after thyroid surgery, the serum calcium levels will be&#xD;
      determined. Low calcium levels can indicate misidentification of parathyroid glands. These&#xD;
      calcium levels are determined only in patients after total thyroidectomy on day 1, 2 and&#xD;
      after two weeks. Also TSH will be determined after two weeks as in standard care. The thyroid&#xD;
      specimen will be send to pathology. In the specimen, the pathologist will search for&#xD;
      parathyroid glands, as is standard care. Furthermore, video recordings will be analyzed,&#xD;
      quantifying the fluorescence signal compared to the background: measuring the Target to&#xD;
      Background Ratio. Also, in these video recordings the time until visualization of the&#xD;
      parathyroid glands will be reassessed by an independent expert.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 23, 2017</start_date>
  <completion_date type="Actual">March 12, 2018</completion_date>
  <primary_completion_date type="Actual">February 1, 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to identification of parathyroid glans</measure>
    <time_frame>during surgery</time_frame>
    <description>Can the parathyroid glands be identified earlier with NIRF light? Time until identification in NIRF and white light will be compared.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total surgical time</measure>
    <time_frame>From incision until closure</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Histology: are parathyroid glands in the specimen? (as in standard care)</measure>
    <time_frame>assessment within 1 week after surgery</time_frame>
    <description>immediately after surgery, the thyroid specimen will be send to the pathology department for histological examination as in standard care, with extra attention on wether there are parathyroid glands in the specimen.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Subjective opinion surgeon about the usefulness of the technique</measure>
    <time_frame>Immediately after surgery</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intra-operative complications due to the use of the technique</measure>
    <time_frame>during surgery</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Quantitative measurement of fluorescence signal related to parathyroid function</measure>
    <time_frame>up to 2 weeks</time_frame>
    <description>Quantitative measurement of fluorescence signal using Target to Background Ratio (TBR) is used, combined with parameters of parathyroid function, namely Calcium levels postoperatively day 1 and day 2, and week 2 in patients after total thyroidectomy (as in standard care), and TSH in patients after total thyroidectomy 2 weeks postoperatively (as in standard care).</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Thyroid Disease</condition>
  <arm_group>
    <arm_group_label>NIRF imaging in thyroid surgery</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>7.5 mg ICG is administered i.v. and the system will be switched to fluorescence mode. If needed, a second dose of 7.5 mg ICG can be administered. After identification of the parathyroid glands, surgery will continue until there is a desire to visualize the parathyroid glands again, another dose of ICG can be given. After complete removal of thyroid, another 7.5 mg of ICG will be given to assess the perfusion of the parathyroid gland. Directly after the procedure the researcher will ask the surgeon whether he/she thinks the technique is feasible.&#xD;
After surgery, the serum calcium levels will be determined in patients after total thyroidectomy on day 1, 2 and after two weeks. TSH will be determined after 2 weeks. The thyroid specimen will be send to pathology. In the specimen, the pathologist will search for parathyroid glands. Video recordings will be analyzed, quantifying the fluorescence signal compared to the background: measuring the TBR.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>NIRF imaging in thyroid surgery</intervention_name>
    <description>a fluorescence imaging system and 7.5 mg of ICG will be used to visualize the parathyroids glands.</description>
    <arm_group_label>NIRF imaging in thyroid surgery</arm_group_label>
    <other_name>Near Infrared Fluorescence Imaging</other_name>
    <other_name>Indocyanine green</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female patients, aged 18 years and above&#xD;
&#xD;
          -  Scheduled for elective total or hemi thyroidectomy&#xD;
&#xD;
          -  Normal liver and renal function&#xD;
&#xD;
          -  No known hypersensitivity for iodine or ICG&#xD;
&#xD;
          -  Able to understand the nature of the study procedures&#xD;
&#xD;
          -  Willing to participate and give written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age &lt; 18 years&#xD;
&#xD;
          -  Liver or renal insufficiency&#xD;
&#xD;
          -  Known ICG, iodine, penicillin or sulfa hypersensitivity&#xD;
&#xD;
          -  Pregnancy or breastfeeding&#xD;
&#xD;
          -  Not able to understand the nature of the study procedure&#xD;
&#xD;
          -  i.v. heparin injection in the last 24h (LMWH not contraindicated)&#xD;
&#xD;
          -  Not willing to participate&#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_official>
    <last_name>Nicole Bouvy, M.D. Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Maastricht University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Maastricht University Medical Center</name>
      <address>
        <city>Maastricht</city>
        <state>Limburg</state>
        <zip>6202</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <verification_date>April 2017</verification_date>
  <study_first_submitted>January 3, 2017</study_first_submitted>
  <study_first_submitted_qc>January 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 6, 2017</study_first_posted>
  <last_update_submitted>March 13, 2018</last_update_submitted>
  <last_update_submitted_qc>March 13, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">March 14, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Near infrared fluorescence</keyword>
  <keyword>ICG</keyword>
  <keyword>Parathyroid gland</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thyroid Diseases</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03012438
org study id: NL57409.068.16
nct id: NCT03012438
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
During surgery in which the thyroid is removed (thyroidectomy), the identification of
      parathyroid glands, that should be saved, can be challenging. Therefore, there is need for
      accurate intraoperative guidance. Earlier animal studies show that the parathyroid glands can
      be identified by the use of the Near Infrared Fluorescent dye Indocyanine green (ICG).

      Our hypothesis is therefore, that the use of ICG-based fluorescence imaging during thyroid
      surgery will provide real-time intraoperative visualization of the parathyroid glands.

      This prospective observational feasibility study aims to evaluate the feasibility of the use
      of ICG in identifying the parathyroid glands during thyroid surgery. 30 patients (age >18
      years) who are already regularly scheduled for thyroid surgery; i.e. patients undergoing
      total thyroidectomy are suitable for inclusion. In all patients, undergoing total
      thyroidectomy infrared fluorescence imaging, using a per-operative intravenous injection of
      7.5 mg ICG, will be tested on feasibility and imaging characteristics.
In this study, the feasibility of the use of NIR fluorescence imaging for the identification
      of the parathyroid glands during thyroid surgery will be explored.

      Per-operatively: The surgery will start as usual. When the surgeon would normally search for
      the parathyroid glands, 7.5 mg of ICG will be administered intravenously through the infusion
      in the patients arm. An intravenous administration is chosen because of the minimal invasive
      nature and results of the described earlier case series in which ICG was also administered
      via peripheral infusion. Directly after that, the fluorescence system can be switched to
      fluorescence mode. The surgeon will determine whether the parathyroid glands are visible now.
      If needed, due to washout, a second dose of 7.5 mg of ICG can be administered. After
      identification of the parathyroid glands, surgery will continue as in the standard situation,
      until there is a desire to visualize the parathyroid glands again, then another dose of ICG
      can be given. Time until first identification of the parathyroid glands and total surgical
      time will be measured. After complete removal of the thyroid, another 7.5 mg of ICG will be
      administered intravenously to visualize the vascularization of the parathyroid gland. The
      intensity will be subjectively scored: 1 parathyroid black after injection of ICG, 2
      partially vascularized, or 3 parathyroid is green; well vascularized. The fluorescence system
      will be used to record the whole procedure. Directly after the procedure the researcher will
      ask the surgeon whether he or she thinks the technique is feasible.

      Postoperatively: As in standard care, after thyroid surgery, the serum calcium levels will be
      determined. Low calcium levels can indicate misidentification of parathyroid glands. These
      calcium levels are determined only in patients after total thyroidectomy on day 1, 2 and
      after two weeks. Also TSH will be determined after two weeks as in standard care. The thyroid
      specimen will be send to pathology. In the specimen, the pathologist will search for
      parathyroid glands, as is standard care. Furthermore, video recordings will be analyzed,
      quantifying the fluorescence signal compared to the background: measuring the Target to
      Background Ratio. Also, in these video recordings the time until visualization of the
      parathyroid glands will be reassessed by an independent expert.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Time to identification of parathyroid glans
time frame: during surgery
description: Can the parathyroid glands be identified earlier with NIRF light? Time until identification in NIRF and white light will be compared.
measure: Total surgical time
time frame: From incision until closure
measure: Histology: are parathyroid glands in the specimen? (as in standard care)
time frame: assessment within 1 week after surgery
description: immediately after surgery, the thyroid specimen will be send to the pathology department for histological examination as in standard care, with extra attention on wether there are parathyroid glands in the specimen.
measure: Subjective opinion surgeon about the usefulness of the technique
time frame: Immediately after surgery
measure: Intra-operative complications due to the use of the technique
time frame: during surgery
measure: Quantitative measurement of fluorescence signal related to parathyroid function
time frame: up to 2 weeks
description: Quantitative measurement of fluorescence signal using Target to Background Ratio (TBR) is used, combined with parameters of parathyroid function, namely Calcium levels postoperatively day 1 and day 2, and week 2 in patients after total thyroidectomy (as in standard care), and TSH in patients after total thyroidectomy 2 weeks postoperatively (as in standard care).
arm group label: NIRF imaging in thyroid surgery
arm group type: Experimental
description: 7.5 mg ICG is administered i.v. and the system will be switched to fluorescence mode. If needed, a second dose of 7.5 mg ICG can be administered. After identification of the parathyroid glands, surgery will continue until there is a desire to visualize the parathyroid glands again, another dose of ICG can be given. After complete removal of thyroid, another 7.5 mg of ICG will be given to assess the perfusion of the parathyroid gland. Directly after the procedure the researcher will ask the surgeon whether he/she thinks the technique is feasible.
After surgery, the serum calcium levels will be determined in patients after total thyroidectomy on day 1, 2 and after two weeks. TSH will be determined after 2 weeks. The thyroid specimen will be send to pathology. In the specimen, the pathologist will search for parathyroid glands. Video recordings will be analyzed, quantifying the fluorescence signal compared to the background: measuring the TBR.
intervention type: Device
intervention name: NIRF imaging in thyroid surgery
description: a fluorescence imaging system and 7.5 mg of ICG will be used to visualize the parathyroids glands.
arm group label: NIRF imaging in thyroid surgery
other name: Near Infrared Fluorescence Imaging
other name: Indocyanine green
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Nicole Bouvy, M.D. Ph.D.
role: Principal Investigator
affiliation: Maastricht University Medical Center
facility: 
country: Netherlands
responsible party type: Sponsor
mesh term: Thyroid Diseases
sharing ipd: No