<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/NCT03013257</url>
  </required_header>
  <id_info>
    <org_study_id>UW 16-565</org_study_id>
    <nct_id>NCT03013257</nct_id>
  </id_info>
  <brief_title>HIFU vs RAI in the Relapsed Graves' Disease</brief_title>
  <official_title>A Randomized, Open-label, Parallel-group Study to Explore the Efficacy of High-intensity Focused Ultrasound (HIFU) Versus Fixed-dose Radioiodine-131 in the Treatment of Relapsed Graves' Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Hong Kong</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>The University of Hong Kong</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>
      Graves' disease (GD) is an autoimmune thyroid disorder caused by stimulating auto-antibodies&#xD;
      to the thyrotrophin (TSH) receptor on thyroid follicular cells. It is the most common cause&#xD;
      of hyperthyroidism and approximately 3% of women and 0.5% of men develop GD in their&#xD;
      lifetime.&#xD;
&#xD;
      RAI has been shown to be a cost-effective and safe therapy in patients with GD but with some&#xD;
      disadvantages. In addition, despite its proven efficacy and safety, many patients do not wish&#xD;
      to undergo RAI because of radiation fear and prefer to either continue ATDs or have surgery.&#xD;
&#xD;
      High-intensity focused ultrasound (HIFU) is a non-invasive procedure that involves the&#xD;
      application of a high-energy focused beam for thermal tissue ablation within a targeted zone.&#xD;
      Similar to the principle of RAI (i.e. using ionizing radiation to ablate thyroid parenchyma&#xD;
      and cause GD remission), we postulated that the heat energy generated from HIFU could also be&#xD;
      used to ablate the thyroid parenchyma and cause GD remission. The idea of using heat energy&#xD;
      to ablate thyroid parenchyma minimally invasively was recently reported using radiofrequency&#xD;
      ablation but to our knowledge, we are one of the first (if not the first) group to propose&#xD;
      using HIFU energy to ablate thyroid parenchyma as a definitive treatment for relapsed GD.&#xD;
&#xD;
      Having obtained ethical approval, a pilot study was conducted to examine the efficacy and&#xD;
      safety of HIFU as a treatment for relapsed GD. In the pilot study, all patients underwent a&#xD;
      safe and successful HIFU ablation for relapsed GD. Based on the results of the pilot study,&#xD;
      we hypothesize that a single HIFU treatment to the thyroid gland may be as effective as our&#xD;
      standard outpatient fixed-dose of RAI (370MBq) in causing remission of GD at 6-month. If our&#xD;
      hypothesis turns out to be true, HIFU could become a treatment option for patients who are&#xD;
      indicated for RAI but do not wish to have it because of one reason or another. HIFU appears&#xD;
      to induce a faster disease remission and lessen the need of deferring pregnancy and radiation&#xD;
      precautions because of the absence of radioactivity.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Graves' disease (GD) is an autoimmune thyroid disorder caused by stimulating auto-antibodies&#xD;
      to the thyrotrophin (thyroid stimulating hormone [TSH]) receptor on thyroid follicular cells.&#xD;
      It is the most common cause of hyperthyroidism and approximately 3% of women and 0.5% of men&#xD;
      develop GD in their lifetime1. In our locality, like Europe and Japan, antithyroid drugs&#xD;
      (ATDs) such as carbimazole or propylthiouracil have been preferred over radioactive iodine&#xD;
      (RAI) and surgery as the initial treatment of GD2-4. This is because ATDs are relatively easy&#xD;
      to administer, could induce disease remission (30-70%) and avoid life-long thyroid hormone&#xD;
      replacement, operative risks and radioactivity2-4. However, because of possible side-effects,&#xD;
      they are only recommended for a period of 12 to 18 months. Taking ATDs for a longer period&#xD;
      does not seem to increase the chance of remission5. Therefore, currently, once the disease&#xD;
      has relapsed after a 18-month of ATD treatment, more definitive treatment modalities like RAI&#xD;
      or surgery are indicated. Regarding to which is more preferable, surgery is usually advised&#xD;
      in patients with large compressive goiter (&gt;80g), suspected or documented thyroid malignancy,&#xD;
      planning to become pregnant within 6 months and moderate to severe Graves' ophthalmopathy&#xD;
      (GO)2-4. As a result, most patients without these conditions are considered for RAI2-4.&#xD;
&#xD;
      RAI has been shown to be a cost-effective and safe therapy in patients with GD4,6,7. In North&#xD;
      America, clinical endocrinologists favor RAI as the initial treatment for GD2-4. However,&#xD;
      since RAI is usually prescribed on an outpatient basis, it is necessary to consider nearby&#xD;
      individuals' exposure doses and formulate radiation precautions carefully8. Other&#xD;
      disadvantages include its slow induction of euthyroidism, potential worsening of GO and&#xD;
      deferral of pregnancy2-4. Although various dosing techniques have been described to ensure an&#xD;
      adequate radiation delivery to the thyroid gland, the simplest and most effective method has&#xD;
      been to administer a fixed dose of RAI2. However, due to local regulations and our&#xD;
      densely-populated areas, administering higher RAI doses (&gt;400MBq) is not permitted on an&#xD;
      outpatient basis9. As a result, the usual RAI dose usually ranges between 185 to 370MBq (i.e.&#xD;
      up to 10mci)10. In addition, despite its proven efficacy and safety, many patients do not&#xD;
      wish to undergo RAI because of radiation fear and prefer to either continue ATDs or have&#xD;
      surgery11.&#xD;
&#xD;
      High-intensity focused ultrasound (HIFU) is a non-invasive procedure that involves the&#xD;
      application of a high-energy focused beam for thermal tissue ablation within a targeted zone.&#xD;
      It has been applied in a variety of medical conditions including uterine fibroids and&#xD;
      prostate, breast, pancreatic, and liver tumors12. Unlike other ablation devices (like&#xD;
      radiofrequency or laser ablation), HIFU does not require needle puncture and is considered&#xD;
      safer and less operator-dependent13. Single HIFU treatment has been shown to reduce size of&#xD;
      benign thyroid nodules13,14. Histologic examination confirmed that HIFU induced complete&#xD;
      tissue necrosis within a targeted area13. Similar to the principle of RAI (i.e. using&#xD;
      ionizing radiation to ablate thyroid parenchyma and cause GD remission), we postulated that&#xD;
      the heat energy generated from HIFU could also be used to ablate the thyroid parenchyma and&#xD;
      cause GD remission. The idea of using heat energy to ablate thyroid parenchyma minimally&#xD;
      invasively was recently reported using radiofrequency ablation15 but to our knowledge, we are&#xD;
      one of the first (if not the first) group to propose using HIFU energy to ablate thyroid&#xD;
      parenchyma as a definitive treatment for relapsed GD.&#xD;
&#xD;
      Having obtained ethical approval, a pilot study was conducted to examine the efficacy and&#xD;
      safety of HIFU as a treatment for relapsed GD. Over a 2-month period, 20 patients underwent a&#xD;
      single HIFU treatment for relapsed GD. The treatment involved ablating the entire right, left&#xD;
      and central (isthmic) lobes with HIFU pulses. To avoid inadvertent injury to heat-sensitive&#xD;
      structures like the recurrent laryngeal nerve, parathyroid glands, trachea and esophagus, we&#xD;
      deliberately left 2-3ml of thyroid parenchyma non-ablated close to the trachea-esophageal&#xD;
      groove on each side. The reason for not leaving a larger amount of non-ablated parenchyma is&#xD;
      because from the experience in subtotal thyroidectomy, leaving &gt; 6ml of normal parenchyma may&#xD;
      diminish the long-term remission rate16.&#xD;
&#xD;
      In the pilot study, all patients underwent a safe and successful HIFU ablation for relapsed&#xD;
      GD. By ultrasound (USG) volumetry, the mean pre-ablation total thyroid volume was 18.5 ±&#xD;
      6.4ml. The average treatment time was 72.7 ± 31.0 mins and the total energy delivered to each&#xD;
      patient was 21.4 ± 5.9 KJ. No patients suffered any major complications afterwards except for&#xD;
      2 patients (10.0%) who had minor neck redness in the first week. By 4-week, all patients were&#xD;
      either biochemically euthyroid (n=15) (without ATDs) or biochemically hypothyroid (requiring&#xD;
      thyroxine replacement) (n=5). At 6-month, 15 (75.0%) patients remained biochemically&#xD;
      euthyroid or hypothyroid without ATDs (i.e. remission) while 5 patients (25.0%) had&#xD;
      biochemical hyperthyroidism. However, of these, only 3 required ATDs and 2 were kept&#xD;
      observed.&#xD;
&#xD;
      Based on the results of the pilot study, we hypothesize that a single HIFU treatment to the&#xD;
      thyroid gland may be as effective as our standard outpatient fixed-dose of RAI (370MBq) in&#xD;
      causing remission of GD at 6-month. If our hypothesis turns out to be true, HIFU could become&#xD;
      a treatment option for patients who are indicated for RAI but do not wish to have it because&#xD;
      of one reason or another. Apart from the benefit of being an outpatient treatment, HIFU&#xD;
      appears to induce a faster disease remission and lessen the need of deferring pregnancy and&#xD;
      radiation precautions because of the absence of radioactivity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 25, 2017</start_date>
  <completion_date type="Actual">June 30, 2020</completion_date>
  <primary_completion_date type="Actual">April 30, 2020</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>Rate of remission</measure>
    <time_frame>6 months</time_frame>
    <description>Stating of biochemically euthyroid and hypothyroid without ATDs after 6 months of treatment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Incidence of treatment-related morbidities from day-0 to post 2-week</measure>
    <time_frame>2 weeks</time_frame>
    <description>To examine any treatment-related morbidities after the treatment within 2 weeks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in auto-antibodies</measure>
    <time_frame>6 months</time_frame>
    <description>To examine the changes of anti-thyroid and TSHR after 6 months of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in total thyroid volume</measure>
    <time_frame>6 months</time_frame>
    <description>To measure the change in size of total thyroid volume after 6 months of treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in eye disease activity</measure>
    <time_frame>6 months</time_frame>
    <description>To examine the change in eye disease activity (CAS) with 6 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Satisfaction score after treatment</measure>
    <time_frame>6 months</time_frame>
    <description>To measure the satisfaction score (1-10) after treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The pain assessment after treatment</measure>
    <time_frame>6 months</time_frame>
    <description>The pain assessment (scoring 1-10) after treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Quality of life</measure>
    <time_frame>6 months</time_frame>
    <description>To examine the change in qualitfy of life with SF-12 scores from baseline to 2-month and 6-month</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The medical costs</measure>
    <time_frame>6 months</time_frame>
    <description>To evaluate the cost of different treatments including direct medical costs (including treatment, investigations, unplanned readmission and visits) and indirect costs (such as number of days before returning to normal activities and work). Medical costs will be based on the latest Government Gazette.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The effectiveness of HIFU treatment</measure>
    <time_frame>6 months</time_frame>
    <description>The effectiveness of HIFU will be quantified by quality-adjusted left years (QALYs), which will be calculated as the product of the average duration of that stage and SF-6D preference value (i.e. from SF-12) for the particular health state.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">240</enrollment>
  <condition>Graves Disease</condition>
  <arm_group>
    <arm_group_label>High Intensity Focused Ultrasound</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Try to use the machine 'Echopulse' with High Intensity Focused Ultrasound to treat the relapsed Graves' disease</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Fixed-dose radioiodine-131</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Using the traditional treatment, fixed-dose radioiodine-131, to treat the relapsed Graves' disease</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Echopulse</intervention_name>
    <description>Replacing HIFU for the Graves' disease patients who traditionally have RAI to remission</description>
    <arm_group_label>High Intensity Focused Ultrasound</arm_group_label>
    <other_name>High Intensity Focused Ultrasound (HIFU)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. A diagnosis of GD based on standard clinical criteria (elevated thyroid hormone&#xD;
             levels, suppressed TSH, positive TSHR auto-antibody, diffuse goiter ± high RAI&#xD;
             uptake).&#xD;
&#xD;
          2. Aged between 18 and 70 years old at the time of informed consent&#xD;
&#xD;
          3. Have had at least one GD relapse. A relapse is defined as recurrent or persistent&#xD;
             hyperthyroidism despite completing a continued course of ATDs for 18 months or more.&#xD;
&#xD;
          4. Indicated for RAI treatment&#xD;
&#xD;
          5. Valid consent is obtained&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prefer or have clear indications for surgery (such as those with large compressive&#xD;
             goiter, suspected or documented thyroid malignancy, wishing to become pregnant within&#xD;
             6 months or with moderate to severe GO).&#xD;
&#xD;
          2. Have pre-existing vocal cord palsy&#xD;
&#xD;
          3. Are unable to move or extend their neck&#xD;
&#xD;
          4. Have either right, left or central (isthmic) lobe measuring &gt;30ml in volume on&#xD;
             pre-treatment USG volumetry (see later)&#xD;
&#xD;
          5. Have concomitant thyroid nodules which are either indeterminate, suspicious of&#xD;
             malignancy or proven malignant on fine needle aspiration cytology (FNAC).&#xD;
&#xD;
          6. Have active or severe Graves ophthalmopathy (GO)&#xD;
&#xD;
          7. Are pregnant, lactating or planning for pregnancy within 6 months&#xD;
&#xD;
          8. Have any medical conditions that would make them too ill to undergo intravenous&#xD;
             sedation or treatment&#xD;
&#xD;
          9. Any condition that is unstable or can jeopardize the safety of the patients and their&#xD;
             compliance to the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hung Hin, Brian Lang, MBBS(Hons)</last_name>
    <role>Principal Investigator</role>
    <affiliation>The University of Hong Kong</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Queen Mary Hospital</name>
      <address>
        <city>Hong Kong</city>
        <zip>852</zip>
        <country>Hong Kong</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Hong Kong</country>
  </location_countries>
  <link>
    <url>http://www.rbhk.org.hk/eng/ordin-cap303.html</url>
    <description>Hong Kong Radiation Ordinance Chapter 303</description>
  </link>
  <link>
    <url>http://www.gld.gov.hk/egazette/english/gazette/toc.php</url>
    <description>Revisions to List of charges: G.N. 1488 to Gazette No. 12/2013</description>
  </link>
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  <verification_date>May 2022</verification_date>
  <study_first_submitted>January 4, 2017</study_first_submitted>
  <study_first_submitted_qc>January 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 6, 2017</study_first_posted>
  <last_update_submitted>May 17, 2022</last_update_submitted>
  <last_update_submitted_qc>May 17, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 18, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The University of Hong Kong</investigator_affiliation>
    <investigator_full_name>Dr. Lang Hung Hin, Brian</investigator_full_name>
    <investigator_title>Clinical Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Relapsed Graves' disease</keyword>
  <keyword>High Intensity Focused Ultrasound</keyword>
  <keyword>RAI</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Graves Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03013257
org study id: UW 16-565
nct id: NCT03013257
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Graves' disease (GD) is an autoimmune thyroid disorder caused by stimulating auto-antibodies
      to the thyrotrophin (TSH) receptor on thyroid follicular cells. It is the most common cause
      of hyperthyroidism and approximately 3% of women and 0.5% of men develop GD in their
      lifetime.

      RAI has been shown to be a cost-effective and safe therapy in patients with GD but with some
      disadvantages. In addition, despite its proven efficacy and safety, many patients do not wish
      to undergo RAI because of radiation fear and prefer to either continue ATDs or have surgery.

      High-intensity focused ultrasound (HIFU) is a non-invasive procedure that involves the
      application of a high-energy focused beam for thermal tissue ablation within a targeted zone.
      Similar to the principle of RAI (i.e. using ionizing radiation to ablate thyroid parenchyma
      and cause GD remission), we postulated that the heat energy generated from HIFU could also be
      used to ablate the thyroid parenchyma and cause GD remission. The idea of using heat energy
      to ablate thyroid parenchyma minimally invasively was recently reported using radiofrequency
      ablation but to our knowledge, we are one of the first (if not the first) group to propose
      using HIFU energy to ablate thyroid parenchyma as a definitive treatment for relapsed GD.

      Having obtained ethical approval, a pilot study was conducted to examine the efficacy and
      safety of HIFU as a treatment for relapsed GD. In the pilot study, all patients underwent a
      safe and successful HIFU ablation for relapsed GD. Based on the results of the pilot study,
      we hypothesize that a single HIFU treatment to the thyroid gland may be as effective as our
      standard outpatient fixed-dose of RAI (370MBq) in causing remission of GD at 6-month. If our
      hypothesis turns out to be true, HIFU could become a treatment option for patients who are
      indicated for RAI but do not wish to have it because of one reason or another. HIFU appears
      to induce a faster disease remission and lessen the need of deferring pregnancy and radiation
      precautions because of the absence of radioactivity.
Graves' disease (GD) is an autoimmune thyroid disorder caused by stimulating auto-antibodies
      to the thyrotrophin (thyroid stimulating hormone [TSH]) receptor on thyroid follicular cells.
      It is the most common cause of hyperthyroidism and approximately 3% of women and 0.5% of men
      develop GD in their lifetime1. In our locality, like Europe and Japan, antithyroid drugs
      (ATDs) such as carbimazole or propylthiouracil have been preferred over radioactive iodine
      (RAI) and surgery as the initial treatment of GD2-4. This is because ATDs are relatively easy
      to administer, could induce disease remission (30-70%) and avoid life-long thyroid hormone
      replacement, operative risks and radioactivity2-4. However, because of possible side-effects,
      they are only recommended for a period of 12 to 18 months. Taking ATDs for a longer period
      does not seem to increase the chance of remission5. Therefore, currently, once the disease
      has relapsed after a 18-month of ATD treatment, more definitive treatment modalities like RAI
      or surgery are indicated. Regarding to which is more preferable, surgery is usually advised
      in patients with large compressive goiter (>80g), suspected or documented thyroid malignancy,
      planning to become pregnant within 6 months and moderate to severe Graves' ophthalmopathy
      (GO)2-4. As a result, most patients without these conditions are considered for RAI2-4.

      RAI has been shown to be a cost-effective and safe therapy in patients with GD4,6,7. In North
      America, clinical endocrinologists favor RAI as the initial treatment for GD2-4. However,
      since RAI is usually prescribed on an outpatient basis, it is necessary to consider nearby
      individuals' exposure doses and formulate radiation precautions carefully8. Other
      disadvantages include its slow induction of euthyroidism, potential worsening of GO and
      deferral of pregnancy2-4. Although various dosing techniques have been described to ensure an
      adequate radiation delivery to the thyroid gland, the simplest and most effective method has
      been to administer a fixed dose of RAI2. However, due to local regulations and our
      densely-populated areas, administering higher RAI doses (>400MBq) is not permitted on an
      outpatient basis9. As a result, the usual RAI dose usually ranges between 185 to 370MBq (i.e.
      up to 10mci)10. In addition, despite its proven efficacy and safety, many patients do not
      wish to undergo RAI because of radiation fear and prefer to either continue ATDs or have
      surgery11.

      High-intensity focused ultrasound (HIFU) is a non-invasive procedure that involves the
      application of a high-energy focused beam for thermal tissue ablation within a targeted zone.
      It has been applied in a variety of medical conditions including uterine fibroids and
      prostate, breast, pancreatic, and liver tumors12. Unlike other ablation devices (like
      radiofrequency or laser ablation), HIFU does not require needle puncture and is considered
      safer and less operator-dependent13. Single HIFU treatment has been shown to reduce size of
      benign thyroid nodules13,14. Histologic examination confirmed that HIFU induced complete
      tissue necrosis within a targeted area13. Similar to the principle of RAI (i.e. using
      ionizing radiation to ablate thyroid parenchyma and cause GD remission), we postulated that
      the heat energy generated from HIFU could also be used to ablate the thyroid parenchyma and
      cause GD remission. The idea of using heat energy to ablate thyroid parenchyma minimally
      invasively was recently reported using radiofrequency ablation15 but to our knowledge, we are
      one of the first (if not the first) group to propose using HIFU energy to ablate thyroid
      parenchyma as a definitive treatment for relapsed GD.

      Having obtained ethical approval, a pilot study was conducted to examine the efficacy and
      safety of HIFU as a treatment for relapsed GD. Over a 2-month period, 20 patients underwent a
      single HIFU treatment for relapsed GD. The treatment involved ablating the entire right, left
      and central (isthmic) lobes with HIFU pulses. To avoid inadvertent injury to heat-sensitive
      structures like the recurrent laryngeal nerve, parathyroid glands, trachea and esophagus, we
      deliberately left 2-3ml of thyroid parenchyma non-ablated close to the trachea-esophageal
      groove on each side. The reason for not leaving a larger amount of non-ablated parenchyma is
      because from the experience in subtotal thyroidectomy, leaving > 6ml of normal parenchyma may
      diminish the long-term remission rate16.

      In the pilot study, all patients underwent a safe and successful HIFU ablation for relapsed
      GD. By ultrasound (USG) volumetry, the mean pre-ablation total thyroid volume was 18.5 ±
      6.4ml. The average treatment time was 72.7 ± 31.0 mins and the total energy delivered to each
      patient was 21.4 ± 5.9 KJ. No patients suffered any major complications afterwards except for
      2 patients (10.0%) who had minor neck redness in the first week. By 4-week, all patients were
      either biochemically euthyroid (n=15) (without ATDs) or biochemically hypothyroid (requiring
      thyroxine replacement) (n=5). At 6-month, 15 (75.0%) patients remained biochemically
      euthyroid or hypothyroid without ATDs (i.e. remission) while 5 patients (25.0%) had
      biochemical hyperthyroidism. However, of these, only 3 required ATDs and 2 were kept
      observed.

      Based on the results of the pilot study, we hypothesize that a single HIFU treatment to the
      thyroid gland may be as effective as our standard outpatient fixed-dose of RAI (370MBq) in
      causing remission of GD at 6-month. If our hypothesis turns out to be true, HIFU could become
      a treatment option for patients who are indicated for RAI but do not wish to have it because
      of one reason or another. Apart from the benefit of being an outpatient treatment, HIFU
      appears to induce a faster disease remission and lessen the need of deferring pregnancy and
      radiation precautions because of the absence of radioactivity.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Rate of remission
time frame: 6 months
description: Stating of biochemically euthyroid and hypothyroid without ATDs after 6 months of treatment
measure: Incidence of treatment-related morbidities from day-0 to post 2-week
time frame: 2 weeks
description: To examine any treatment-related morbidities after the treatment within 2 weeks.
measure: Change in auto-antibodies
time frame: 6 months
description: To examine the changes of anti-thyroid and TSHR after 6 months of treatment
measure: Change in total thyroid volume
time frame: 6 months
description: To measure the change in size of total thyroid volume after 6 months of treatment
measure: Change in eye disease activity
time frame: 6 months
description: To examine the change in eye disease activity (CAS) with 6 months.
measure: Satisfaction score after treatment
time frame: 6 months
description: To measure the satisfaction score (1-10) after treatment
measure: The pain assessment after treatment
time frame: 6 months
description: The pain assessment (scoring 1-10) after treatment
measure: Change in Quality of life
time frame: 6 months
description: To examine the change in qualitfy of life with SF-12 scores from baseline to 2-month and 6-month
measure: The medical costs
time frame: 6 months
description: To evaluate the cost of different treatments including direct medical costs (including treatment, investigations, unplanned readmission and visits) and indirect costs (such as number of days before returning to normal activities and work). Medical costs will be based on the latest Government Gazette.
measure: The effectiveness of HIFU treatment
time frame: 6 months
description: The effectiveness of HIFU will be quantified by quality-adjusted left years (QALYs), which will be calculated as the product of the average duration of that stage and SF-6D preference value (i.e. from SF-12) for the particular health state.
arm group label: High Intensity Focused Ultrasound
arm group type: Experimental
description: Try to use the machine 'Echopulse' with High Intensity Focused Ultrasound to treat the relapsed Graves' disease
arm group label: Fixed-dose radioiodine-131
arm group type: No Intervention
description: Using the traditional treatment, fixed-dose radioiodine-131, to treat the relapsed Graves' disease
intervention type: Device
intervention name: Echopulse
description: Replacing HIFU for the Graves' disease patients who traditionally have RAI to remission
arm group label: High Intensity Focused Ultrasound
other name: High Intensity Focused Ultrasound (HIFU)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Hung Hin, Brian Lang, MBBS(Hons)
role: Principal Investigator
affiliation: The University of Hong Kong
facility: 
country: Hong Kong
url: http://www.rbhk.org.hk/eng/ordin-cap303.html
description: Hong Kong Radiation Ordinance Chapter 303
url: http://www.gld.gov.hk/egazette/english/gazette/toc.php
description: Revisions to List of charges: G.N. 1488 to Gazette No. 12/2013
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PMID: 23421407
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PMID: 21510801
citation: Burch HB, Cooper DS. Management of Graves Disease: A Review. JAMA. 2015 Dec 15;314(23):2544-54. doi: 10.1001/jama.2015.16535. Erratum In: JAMA. 2016 Feb 9;315(6):614.
PMID: 26670972
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PMID: 22394559
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PMID: 16189168
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PMID: 23824415
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PMID: 16839261
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PMID: 26046966
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PMID: 19652233
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PMID: 21683939
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PMID: 21603311
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PMID: 19803790
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PMID: 25768327
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PMID: 10792958
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PMID: 22999130
responsible party type: Principal Investigator
investigator affiliation: The University of Hong Kong
investigator full name: Dr. Lang Hung Hin, Brian
investigator title: Clinical Associate Professor
mesh term: Graves Disease
sharing ipd: Undecided