<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/NCT03303053</url>
  </required_header>
  <id_info>
    <org_study_id>ChoPS Study Version 3.0</org_study_id>
    <nct_id>NCT03303053</nct_id>
  </id_info>
  <brief_title>Efficacy and Safety of Cholestyramine and Prednisolone as Adjunctive Therapy in Treatment of Overt Hyperthyroidism</brief_title>
  <acronym>ChoPS</acronym>
  <official_title>A Multi-center, Open Label, Randomised Parallel- Group Study to Compare the Efficacy of Cholestyramine Plus Standard Treatment Versus Prednisolone Plus Standard Treatment Versus Standard Treatment Alone in Treatment of Overt Hyperthyroidism</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Clinical Research Centre, Malaysia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ministry of Health, Malaysia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Clinical Research Centre, Malaysia</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Hyperthyroidism is the second most common endocrine disorder in the world with Graves'&#xD;
      disease being the commonest. Anti thyroid drugs including methimazole, carbimazole, and&#xD;
      propylthiouracil are effective treatments but take in most cases between 6 to 8 weeks to&#xD;
      achieve euthyroidism. This study aim to assess the efficacy of cholestyramine and&#xD;
      prednisolone as adjunctive treatment to standard treatment in patients with overt&#xD;
      hyperthyroidism in 4 weeks.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Hyperthyroidism is the second most common endocrine disorder in the world with an estimate&#xD;
      prevalence rate of 0.5-1.3% with Graves' disease being the commonest cause.&#xD;
&#xD;
      Uncontrolled hyperthyroidism results in increase cardiovascular morbidity and mortality&#xD;
      primarily due to heart failure and thromboembolism. Therefore treatment is essential to&#xD;
      restore a euthyroid state in order to reverse the cardiovascular complications.&#xD;
&#xD;
      Anti thyroid drugs (ATDs) including methimazole, carbimazole, and propylthiouracil are&#xD;
      effective treatments that inhibit thyroid hormone synthesis, and have clinically important&#xD;
      immunosuppressive effects including reducing serum antithyrotropin receptor antibody (TRAb)&#xD;
      concentration with time but take in most cases between 6 to 8 weeks to achieve euthyroidism.&#xD;
      Therefore there may be a role for adjunctive treatment added on to ATDs. It may be situations&#xD;
      where adjunctive treatment is required to alleviate symptoms and restore euthyroidism rapidly&#xD;
      such as before surgery or radioactive iodine treatment or in vulnerable groups such as the&#xD;
      elderly or those with serious thyrotoxic complications.&#xD;
&#xD;
      This study aim to assess the efficacy of cholestyramine and prednisolone as adjunctive&#xD;
      treatment to standard treatment in patients with overt hyperthyroidism in 4 weeks.&#xD;
      Cholestyramine is an anion exchange resin that binds thyroxine (T4) in the intestine&#xD;
      resulting in fecal excretion of T4 thus reducing the enterohepatic circulation and absorption&#xD;
      in hyperthyroidism. Steroids have been shown to be effective in controlling hyperthyroidism&#xD;
      by inhibiting the conversion of thyroxine to triiodothyronine peripherally and also blocks&#xD;
      the release of thyroxine from the thyroid gland. It may also have the potential to suppress&#xD;
      the immune response and hence decrease stimulation of the thyroid gland in Graves.&#xD;
&#xD;
      135 patients with moderate to severe uncontrolled overt hyperthyroid patients secondary to&#xD;
      Graves disease will be randomized into 3 groups. Group 1 patients will be treated with&#xD;
      cholestyramine 4g twice a day plus carbimazole and propanolol for 4 weeks. Group 2 patients&#xD;
      will be treated with prednisolone 30 mg daily for week 1, 20 mg daily for week 2, 10 mg daily&#xD;
      for week 3 and 5 mg daily for week 4 plus carbimazole and propanolol for 4 weeks. Group 3&#xD;
      patients will be treated with carbimazole 30 mg daily and propanolol 40 mg bd for 4 weeks.&#xD;
      Patients will have their clinical status (weight, blood pressure, pulse rate) measured at&#xD;
      baseline along with a TRAb level and Free Triiodotyronine (T3), Free T4 and Thyroid&#xD;
      stimulating hormone (TSH) levels. They will be evaluated at week 2 and week 4 of intervention&#xD;
      period and have their clinical status (weight, blood pressure, pulse rate) and laboratory&#xD;
      (Free T3, Free T4, TSH, Potassium, Fasting/random blood glucose) measured. Adverse events&#xD;
      will be monitored at week 2, 4, and 6.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">May 11, 2017</start_date>
  <completion_date type="Anticipated">March 1, 2018</completion_date>
  <primary_completion_date type="Anticipated">March 1, 2018</primary_completion_date>
  <phase>Phase 3</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>Multi-center, open label, randomised, parallel-group</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of patients whose Free T4 normalize between the groups</measure>
    <time_frame>4 weeks</time_frame>
    <description>Normal Free T4 is defined as Free T4 level between 9-25 pmol/L</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of patients whose Free T3 normalize between the groups</measure>
    <time_frame>4 weeks</time_frame>
    <description>Normal free T3 is defined as Free T3 level between 3.5-6.5 pmol/L</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adverse events between the groups</measure>
    <time_frame>6 weeks</time_frame>
    <description>Number of adverse events between the groups</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction in Free T4 levels</measure>
    <time_frame>4 weeks</time_frame>
    <description>Reduction in Free T4 levels ( Change from baseline within 4 weeks)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reduction in Free T3 levels</measure>
    <time_frame>4 weeks</time_frame>
    <description>Reduction in Free T3 levels (Change from baseline within 4 weeks)</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">135</enrollment>
  <condition>Hyperthyroidism</condition>
  <condition>Graves Disease</condition>
  <arm_group>
    <arm_group_label>Group1:Cholestyramine+standard treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cholestyramine powder 4g twice daily, Tablet Carbimazole 30 mg daily, Tablet propanolol 40 mg twice daily for 4 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group2:Prednisolone+standard treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tablet prednisolone 30 mg daily for week 1, 20 mg daily for week 2, 10 mg daily for week 3 and 5 mg daily for week 4, Tablet carbimazole 30 mg daily, Tablet propanolol 40 mg twice daily for 4 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group 3: Standard treatment alone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Carbimazole 30 mg daily and propanolol 40 mg twice daily for 4 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cholestyramine Powder 4g</intervention_name>
    <description>Cholestyramine powder 4g twice daily, Tablet Carbimazole 30 mg daily, Tablet propanolol 40 mg twice daily for 4 weeks</description>
    <arm_group_label>Group1:Cholestyramine+standard treatment</arm_group_label>
    <other_name>Questran</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Prednisolone</intervention_name>
    <description>Tablet prednisolone 30 mg daily for week 1, 20 mg daily for week 2, 10 mg daily for week 3 and 5 mg daily for week 4, Tablet carbimazole 30 mg daily, Tablet propanolol 40 mg twice daily for 4 weeks</description>
    <arm_group_label>Group2:Prednisolone+standard treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Standard treatment</intervention_name>
    <description>Carbimazole 30 mg daily and propanolol 40 mg twice daily for 4 weeks</description>
    <arm_group_label>Group 3: Standard treatment alone</arm_group_label>
    <other_name>Carbimazole + Propanolol</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Provision of written consent by subject or guardian.&#xD;
&#xD;
          2. Subject of either sex, more than 18 years of age&#xD;
&#xD;
          3. Subjects with moderate to severe overt hyperthyroidism (caused by Graves' disease).&#xD;
&#xD;
               -  Moderate to severe overt hyperthyroidism is defined as Free T4&gt; 1.5 times upper&#xD;
                  limit of normal reference range and TSH below lower limit of reference range, who&#xD;
                  are either newly diagnosed or previously diagnosed and receiving ATDs currently.&#xD;
&#xD;
               -  Graves disease is defined as hyperthyroidism coupled with clinical signs of&#xD;
                  symmetrical diffuse goiter, thyroid orbitopathy, or diffuse and vascular thyroid&#xD;
                  on ultrasound or positive TRAb antibody&#xD;
&#xD;
          4. Female patients will either be&#xD;
&#xD;
               -  post-menopausal for &gt; 2 years&#xD;
&#xD;
               -  Women of childbearing potential can be included if surgically sterile or using&#xD;
                  double contraception with at least one method being barrier contraception. Women&#xD;
                  of childbearing potential must have a negative pregnancy test at screening and at&#xD;
                  randomisation. Pregnancy tests will be repeated during each visit.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Inability or unwillingness to provide written consent.&#xD;
&#xD;
          2. Inability or unwillingness to comply with the requirements of the protocol as&#xD;
             determined by the investigator.&#xD;
&#xD;
          3. Pregnancy, breastfeeding or use of non-reliable method of contraception.&#xD;
&#xD;
          4. Subjects with history of chronic liver disease, chronic renal failure, heart failure,&#xD;
             diabetes mellitus&#xD;
&#xD;
          5. Subjects with history of peptic ulcer disease, upper gastrointestinal bleeding,&#xD;
             diverticulitis or ulcerative colitis.&#xD;
&#xD;
          6. Subjects who have recently had live or attenuated virus vaccines&#xD;
&#xD;
          7. Subjects with current infection (systemic fungal, active tuberculosis, cerebral&#xD;
             malaria, viral hepatitis, HIV)&#xD;
&#xD;
          8. Subjects with cataracts and glaucoma&#xD;
&#xD;
          9. Subjects with osteoporosis&#xD;
&#xD;
         10. Subjects with psychiatric disorders&#xD;
&#xD;
         11. Subjects with complete biliary obstruction, bleeding disorders, hypertriglyceridemia&#xD;
             (fasting triglyceride levels &gt; 300mg/dL)&#xD;
&#xD;
         12. Previous history of adverse reactions to cholestyramine or other bile acid&#xD;
             sequestrants&#xD;
&#xD;
         13. Previous history of adverse reactions to prednisolone or other steroid compound&#xD;
&#xD;
         14. Current use of cholestyramine or prednisolone or other steroid compound&#xD;
&#xD;
         15. Participation in another clinical trial and/or receipt of cholestyramine or&#xD;
             prednisolone within 4 weeks prior to screening visit.&#xD;
&#xD;
         16. Subjects with history of bronchial asthma, bronchospasm, peripheral vascular disease&#xD;
             or adverse reactions to propanolol&#xD;
&#xD;
         17. Subjects with adverse reactions to carbimazole&#xD;
&#xD;
         18. Hypokalemia (serum K+ &lt;3.5 mmol/L)&#xD;
&#xD;
         19. Thyroid storm defined as Burch Wartofsky Score &gt;45&#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>Serena SK Khoo, Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>HospitalPutrajaya</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Serena SK Khoo, Dr.</last_name>
    <phone>+603 83124200</phone>
    <email>sk_liv@rocketmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Zanariah Hussein, Dr.</last_name>
    <phone>+03 83124200</phone>
    <email>zanariahh@hotmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Hospital Queen Elizabeth 2</name>
      <address>
        <city>Kota Kinabalu</city>
        <state>Sabah</state>
        <zip>88300</zip>
        <country>Malaysia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yin Khet Fung, Dr.</last_name>
      <phone>+6 088324600</phone>
      <email>fung@doctors.org.uk</email>
    </contact>
    <contact_backup>
      <last_name>Gayathri D Krishnan, Dr.</last_name>
      <phone>+6 088324600</phone>
      <email>kgaya3@yahoo.com</email>
    </contact_backup>
    <investigator>
      <last_name>Pei Lin Chan, Dr.</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Ampang</name>
      <address>
        <city>Ampang</city>
        <state>Selangor</state>
        <zip>68000</zip>
        <country>Malaysia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Vijiya M Valayatham, Dr</last_name>
      <phone>+60342896000</phone>
      <email>ammu_vj@yahoo.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Putrajaya</name>
      <address>
        <city>Putrajaya</city>
        <state>Wilayah Persekutuan</state>
        <zip>62250</zip>
        <country>Malaysia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Serena SK Khoo, Dr.</last_name>
      <phone>+6 03 83124200</phone>
      <email>sk_liv@rocketmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Zanariah Hussein, Dr.</last_name>
      <phone>+6 03 83124200</phone>
      <email>zanariahh@hotmail.com</email>
    </contact_backup>
    <investigator>
      <last_name>Siti A Alias, Dr</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Lisa Mohamed Nor, Dr</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Rashidah Bahari, Dr</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Nurul Z Badarudin, Dr</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Malaysia</country>
  </location_countries>
  <reference>
    <citation>Nakamura H, Noh JY, Itoh K, Fukata S, Miyauchi A, Hamada N. Comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by Graves' disease. J Clin Endocrinol Metab. 2007 Jun;92(6):2157-62. doi: 10.1210/jc.2006-2135. Epub 2007 Mar 27.</citation>
    <PMID>17389704</PMID>
  </reference>
  <reference>
    <citation>Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002 Feb;87(2):489-99. doi: 10.1210/jcem.87.2.8182.</citation>
    <PMID>11836274</PMID>
  </reference>
  <reference>
    <citation>Garmendia Madariaga A, Santos Palacios S, Guillen-Grima F, Galofre JC. The incidence and prevalence of thyroid dysfunction in Europe: a meta-analysis. J Clin Endocrinol Metab. 2014 Mar;99(3):923-31. doi: 10.1210/jc.2013-2409. Epub 2014 Jan 1.</citation>
    <PMID>24423323</PMID>
  </reference>
  <reference>
    <citation>Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL, Rivkees SA, Samuels M, Sosa JA, Stan MN, Walter MA. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016 Oct;26(10):1343-1421. doi: 10.1089/thy.2016.0229. Erratum In: Thyroid. 2017 Nov;27(11):1462.</citation>
    <PMID>27521067</PMID>
  </reference>
  <reference>
    <citation>Dahl P, Danzi S, Klein I. Thyrotoxic cardiac disease. Curr Heart Fail Rep. 2008 Sep;5(3):170-6. doi: 10.1007/s11897-008-0026-9.</citation>
    <PMID>18752767</PMID>
  </reference>
  <reference>
    <citation>Frost L, Vestergaard P, Mosekilde L. Hyperthyroidism and risk of atrial fibrillation or flutter: a population-based study. Arch Intern Med. 2004 Aug 9-23;164(15):1675-8. doi: 10.1001/archinte.164.15.1675. Erratum In: Arch Intern Med. 2005 Feb 14;165(3):307.</citation>
    <PMID>15302638</PMID>
  </reference>
  <reference>
    <citation>Sundaresh V, Brito JP, Wang Z, Prokop LJ, Stan MN, Murad MH, Bahn RS. Comparative effectiveness of therapies for Graves' hyperthyroidism: a systematic review and network meta-analysis. J Clin Endocrinol Metab. 2013 Sep;98(9):3671-7. doi: 10.1210/jc.2013-1954. Epub 2013 Jul 3.</citation>
    <PMID>23824415</PMID>
  </reference>
  <reference>
    <citation>Kaykhaei MA, Shams M, Sadegholvad A, Dabbaghmanesh MH, Omrani GR. Low doses of cholestyramine in the treatment of hyperthyroidism. Endocrine. 2008 Aug-Dec;34(1-3):52-5. doi: 10.1007/s12020-008-9107-5. Epub 2008 Oct 23.</citation>
    <PMID>18946743</PMID>
  </reference>
  <reference>
    <citation>Migneco A, Ojetti V, Testa A, De Lorenzo A, Gentiloni Silveri N. Management of thyrotoxic crisis. Eur Rev Med Pharmacol Sci. 2005 Jan-Feb;9(1):69-74.</citation>
    <PMID>15850146</PMID>
  </reference>
  <reference>
    <citation>Solomon BL, Wartofsky L, Burman KD. Adjunctive cholestyramine therapy for thyrotoxicosis. Clin Endocrinol (Oxf). 1993 Jan;38(1):39-43. doi: 10.1111/j.1365-2265.1993.tb00970.x.</citation>
    <PMID>8435884</PMID>
  </reference>
  <reference>
    <citation>Mercado M, Mendoza-Zubieta V, Bautista-Osorio R, Espinoza-de los Monteros AL. Treatment of hyperthyroidism with a combination of methimazole and cholestyramine. J Clin Endocrinol Metab. 1996 Sep;81(9):3191-3. doi: 10.1210/jcem.81.9.8784067.</citation>
    <PMID>8784067</PMID>
  </reference>
  <reference>
    <citation>Jude EB, Dale J, Kumar S, Dodson PM. Treatment of thyrotoxicosis resistant to carbimazole with corticosteroids. Postgrad Med J. 1996 Aug;72(850):489-91. doi: 10.1136/pgmj.72.850.489.</citation>
    <PMID>8796215</PMID>
  </reference>
  <reference>
    <citation>Baeza A, Aguayo J, Barria M, Pineda G. Rapid preoperative preparation in hyperthyroidism. Clin Endocrinol (Oxf). 1991 Nov;35(5):439-42. doi: 10.1111/j.1365-2265.1991.tb03562.x.</citation>
    <PMID>1814659</PMID>
  </reference>
  <reference>
    <citation>Page SR, Sheard CE, Herbert M, Hopton M, Jeffcoate WJ. A comparison of 20 or 40 mg per day of carbimazole in the initial treatment of hyperthyroidism. Clin Endocrinol (Oxf). 1996 Nov;45(5):511-6. doi: 10.1046/j.1365-2265.1996.00800.x. Erratum In: Clin Endocrinol (Oxf) 1997 Feb;46(2):240.</citation>
    <PMID>8977745</PMID>
  </reference>
  <reference>
    <citation>Ozawa Y, Daida H, Shimizu T, Shishiba Y. Rapid improvement of thyroid function by using glucocorticoid indicated for the preoperative preparation of subtotal thyroidectomy in Graves' disease. Endocrinol Jpn. 1983 Feb;30(1):93-100. doi: 10.1507/endocrj1954.30.93.</citation>
    <PMID>6688394</PMID>
  </reference>
  <reference>
    <citation>Conn HO, Poynard T. Corticosteroids and peptic ulcer: meta-analysis of adverse events during steroid therapy. J Intern Med. 1994 Dec;236(6):619-32. doi: 10.1111/j.1365-2796.1994.tb00855.x.</citation>
    <PMID>7989897</PMID>
  </reference>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>September 13, 2017</study_first_submitted>
  <study_first_submitted_qc>October 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 5, 2017</study_first_posted>
  <last_update_submitted>October 1, 2017</last_update_submitted>
  <last_update_submitted_qc>October 1, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 5, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hyperthyroidism,Graves disease,Cholestyramine,Prednisolone</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Graves Disease</mesh_term>
    <mesh_term>Hyperthyroidism</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Prednisolone</mesh_term>
    <mesh_term>Cholestyramine Resin</mesh_term>
    <mesh_term>Carbimazole</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 5, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/53/NCT03303053/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 5, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/53/NCT03303053/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03303053
org study id: ChoPS Study Version 3.0
nct id: NCT03303053
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Hyperthyroidism is the second most common endocrine disorder in the world with Graves'
      disease being the commonest. Anti thyroid drugs including methimazole, carbimazole, and
      propylthiouracil are effective treatments but take in most cases between 6 to 8 weeks to
      achieve euthyroidism. This study aim to assess the efficacy of cholestyramine and
      prednisolone as adjunctive treatment to standard treatment in patients with overt
      hyperthyroidism in 4 weeks.
Hyperthyroidism is the second most common endocrine disorder in the world with an estimate
      prevalence rate of 0.5-1.3% with Graves' disease being the commonest cause.

      Uncontrolled hyperthyroidism results in increase cardiovascular morbidity and mortality
      primarily due to heart failure and thromboembolism. Therefore treatment is essential to
      restore a euthyroid state in order to reverse the cardiovascular complications.

      Anti thyroid drugs (ATDs) including methimazole, carbimazole, and propylthiouracil are
      effective treatments that inhibit thyroid hormone synthesis, and have clinically important
      immunosuppressive effects including reducing serum antithyrotropin receptor antibody (TRAb)
      concentration with time but take in most cases between 6 to 8 weeks to achieve euthyroidism.
      Therefore there may be a role for adjunctive treatment added on to ATDs. It may be situations
      where adjunctive treatment is required to alleviate symptoms and restore euthyroidism rapidly
      such as before surgery or radioactive iodine treatment or in vulnerable groups such as the
      elderly or those with serious thyrotoxic complications.

      This study aim to assess the efficacy of cholestyramine and prednisolone as adjunctive
      treatment to standard treatment in patients with overt hyperthyroidism in 4 weeks.
      Cholestyramine is an anion exchange resin that binds thyroxine (T4) in the intestine
      resulting in fecal excretion of T4 thus reducing the enterohepatic circulation and absorption
      in hyperthyroidism. Steroids have been shown to be effective in controlling hyperthyroidism
      by inhibiting the conversion of thyroxine to triiodothyronine peripherally and also blocks
      the release of thyroxine from the thyroid gland. It may also have the potential to suppress
      the immune response and hence decrease stimulation of the thyroid gland in Graves.

      135 patients with moderate to severe uncontrolled overt hyperthyroid patients secondary to
      Graves disease will be randomized into 3 groups. Group 1 patients will be treated with
      cholestyramine 4g twice a day plus carbimazole and propanolol for 4 weeks. Group 2 patients
      will be treated with prednisolone 30 mg daily for week 1, 20 mg daily for week 2, 10 mg daily
      for week 3 and 5 mg daily for week 4 plus carbimazole and propanolol for 4 weeks. Group 3
      patients will be treated with carbimazole 30 mg daily and propanolol 40 mg bd for 4 weeks.
      Patients will have their clinical status (weight, blood pressure, pulse rate) measured at
      baseline along with a TRAb level and Free Triiodotyronine (T3), Free T4 and Thyroid
      stimulating hormone (TSH) levels. They will be evaluated at week 2 and week 4 of intervention
      period and have their clinical status (weight, blood pressure, pulse rate) and laboratory
      (Free T3, Free T4, TSH, Potassium, Fasting/random blood glucose) measured. Adverse events
      will be monitored at week 2, 4, and 6.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Multi-center, open label, randomised, parallel-group
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of patients whose Free T4 normalize between the groups
time frame: 4 weeks
description: Normal Free T4 is defined as Free T4 level between 9-25 pmol/L
measure: Percentage of patients whose Free T3 normalize between the groups
time frame: 4 weeks
description: Normal free T3 is defined as Free T3 level between 3.5-6.5 pmol/L
measure: Adverse events between the groups
time frame: 6 weeks
description: Number of adverse events between the groups
measure: Reduction in Free T4 levels
time frame: 4 weeks
description: Reduction in Free T4 levels ( Change from baseline within 4 weeks)
measure: Reduction in Free T3 levels
time frame: 4 weeks
description: Reduction in Free T3 levels (Change from baseline within 4 weeks)
arm group label: Group1:Cholestyramine+standard treatment
arm group type: Experimental
description: Cholestyramine powder 4g twice daily, Tablet Carbimazole 30 mg daily, Tablet propanolol 40 mg twice daily for 4 weeks
arm group label: Group2:Prednisolone+standard treatment
arm group type: Experimental
description: Tablet prednisolone 30 mg daily for week 1, 20 mg daily for week 2, 10 mg daily for week 3 and 5 mg daily for week 4, Tablet carbimazole 30 mg daily, Tablet propanolol 40 mg twice daily for 4 weeks
arm group label: Group 3: Standard treatment alone
arm group type: Active Comparator
description: Carbimazole 30 mg daily and propanolol 40 mg twice daily for 4 weeks
intervention type: Drug
intervention name: Cholestyramine Powder 4g
description: Cholestyramine powder 4g twice daily, Tablet Carbimazole 30 mg daily, Tablet propanolol 40 mg twice daily for 4 weeks
arm group label: Group1:Cholestyramine+standard treatment
other name: Questran
intervention type: Drug
intervention name: Prednisolone
description: Tablet prednisolone 30 mg daily for week 1, 20 mg daily for week 2, 10 mg daily for week 3 and 5 mg daily for week 4, Tablet carbimazole 30 mg daily, Tablet propanolol 40 mg twice daily for 4 weeks
arm group label: Group2:Prednisolone+standard treatment
intervention type: Drug
intervention name: Standard treatment
description: Carbimazole 30 mg daily and propanolol 40 mg twice daily for 4 weeks
arm group label: Group 3: Standard treatment alone
other name: Carbimazole + Propanolol
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Serena SK Khoo, Dr.
role: Principal Investigator
affiliation: HospitalPutrajaya
last name: Serena SK Khoo, Dr.
phone: +603 83124200
email: sk_liv@rocketmail.com
last name: Zanariah Hussein, Dr.
phone: +03 83124200
email: zanariahh@hotmail.com
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
investigator: 
country: Malaysia
citation: Nakamura H, Noh JY, Itoh K, Fukata S, Miyauchi A, Hamada N. Comparison of methimazole and propylthiouracil in patients with hyperthyroidism caused by Graves' disease. J Clin Endocrinol Metab. 2007 Jun;92(6):2157-62. doi: 10.1210/jc.2006-2135. Epub 2007 Mar 27.
PMID: 17389704
citation: Hollowell JG, Staehling NW, Flanders WD, Hannon WH, Gunter EW, Spencer CA, Braverman LE. Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab. 2002 Feb;87(2):489-99. doi: 10.1210/jcem.87.2.8182.
PMID: 11836274
citation: Garmendia Madariaga A, Santos Palacios S, Guillen-Grima F, Galofre JC. The incidence and prevalence of thyroid dysfunction in Europe: a meta-analysis. J Clin Endocrinol Metab. 2014 Mar;99(3):923-31. doi: 10.1210/jc.2013-2409. Epub 2014 Jan 1.
PMID: 24423323
citation: Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL, Rivkees SA, Samuels M, Sosa JA, Stan MN, Walter MA. 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis. Thyroid. 2016 Oct;26(10):1343-1421. doi: 10.1089/thy.2016.0229. Erratum In: Thyroid. 2017 Nov;27(11):1462.
PMID: 27521067
citation: Dahl P, Danzi S, Klein I. Thyrotoxic cardiac disease. Curr Heart Fail Rep. 2008 Sep;5(3):170-6. doi: 10.1007/s11897-008-0026-9.
PMID: 18752767
citation: Frost L, Vestergaard P, Mosekilde L. Hyperthyroidism and risk of atrial fibrillation or flutter: a population-based study. Arch Intern Med. 2004 Aug 9-23;164(15):1675-8. doi: 10.1001/archinte.164.15.1675. Erratum In: Arch Intern Med. 2005 Feb 14;165(3):307.
PMID: 15302638
citation: Sundaresh V, Brito JP, Wang Z, Prokop LJ, Stan MN, Murad MH, Bahn RS. Comparative effectiveness of therapies for Graves' hyperthyroidism: a systematic review and network meta-analysis. J Clin Endocrinol Metab. 2013 Sep;98(9):3671-7. doi: 10.1210/jc.2013-1954. Epub 2013 Jul 3.
PMID: 23824415
citation: Kaykhaei MA, Shams M, Sadegholvad A, Dabbaghmanesh MH, Omrani GR. Low doses of cholestyramine in the treatment of hyperthyroidism. Endocrine. 2008 Aug-Dec;34(1-3):52-5. doi: 10.1007/s12020-008-9107-5. Epub 2008 Oct 23.
PMID: 18946743
citation: Migneco A, Ojetti V, Testa A, De Lorenzo A, Gentiloni Silveri N. Management of thyrotoxic crisis. Eur Rev Med Pharmacol Sci. 2005 Jan-Feb;9(1):69-74.
PMID: 15850146
citation: Solomon BL, Wartofsky L, Burman KD. Adjunctive cholestyramine therapy for thyrotoxicosis. Clin Endocrinol (Oxf). 1993 Jan;38(1):39-43. doi: 10.1111/j.1365-2265.1993.tb00970.x.
PMID: 8435884
citation: Mercado M, Mendoza-Zubieta V, Bautista-Osorio R, Espinoza-de los Monteros AL. Treatment of hyperthyroidism with a combination of methimazole and cholestyramine. J Clin Endocrinol Metab. 1996 Sep;81(9):3191-3. doi: 10.1210/jcem.81.9.8784067.
PMID: 8784067
citation: Jude EB, Dale J, Kumar S, Dodson PM. Treatment of thyrotoxicosis resistant to carbimazole with corticosteroids. Postgrad Med J. 1996 Aug;72(850):489-91. doi: 10.1136/pgmj.72.850.489.
PMID: 8796215
citation: Baeza A, Aguayo J, Barria M, Pineda G. Rapid preoperative preparation in hyperthyroidism. Clin Endocrinol (Oxf). 1991 Nov;35(5):439-42. doi: 10.1111/j.1365-2265.1991.tb03562.x.
PMID: 1814659
citation: Page SR, Sheard CE, Herbert M, Hopton M, Jeffcoate WJ. A comparison of 20 or 40 mg per day of carbimazole in the initial treatment of hyperthyroidism. Clin Endocrinol (Oxf). 1996 Nov;45(5):511-6. doi: 10.1046/j.1365-2265.1996.00800.x. Erratum In: Clin Endocrinol (Oxf) 1997 Feb;46(2):240.
PMID: 8977745
citation: Ozawa Y, Daida H, Shimizu T, Shishiba Y. Rapid improvement of thyroid function by using glucocorticoid indicated for the preoperative preparation of subtotal thyroidectomy in Graves' disease. Endocrinol Jpn. 1983 Feb;30(1):93-100. doi: 10.1507/endocrj1954.30.93.
PMID: 6688394
citation: Conn HO, Poynard T. Corticosteroids and peptic ulcer: meta-analysis of adverse events during steroid therapy. J Intern Med. 1994 Dec;236(6):619-32. doi: 10.1111/j.1365-2796.1994.tb00855.x.
PMID: 7989897
responsible party type: Sponsor
mesh term: Graves Disease
mesh term: Hyperthyroidism
mesh term: Prednisolone
mesh term: Cholestyramine Resin
mesh term: Carbimazole
sharing ipd: Undecided
provided document: 
provided document: 