<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/NCT02201602</url>
  </required_header>
  <id_info>
    <org_study_id>Gliclazide</org_study_id>
    <nct_id>NCT02201602</nct_id>
  </id_info>
  <brief_title>Sulphonylurea Receptor Mutation and Responsiveness to Gliclazide - a Pilot Proof of Concept, Randomised Cross-over Study</brief_title>
  <official_title>Sulphonylurea Receptor Mutation and Responsiveness to Gliclazide - a Pilot Proof of Concept, Randomised Cross-over Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Khoo Teck Puat Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Khoo Teck Puat Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Gliclazide has greater glucose lowering efficacy than glibenclamide among type 2 diabetes&#xD;
      mellitus patients with minor haplotype (K23/A1369) at the KCNJ11/ABCC gene locations.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Sulphonylurea (SU) is a glucose-lowering agent used widely to treat type 2 diabetes mellitus&#xD;
      (T2DM). SU promotes insulin secretion from the pancreatic islet beta cell via binding and&#xD;
      inhibition of the ATP-sensitive potassium (KATP) channel. The KATP channel is made up of two&#xD;
      subcomponents, an inner Kir6.2 K+ channel (coded by the KCNJ11 gene) and an outer SU receptor&#xD;
      1 (SUR1) (coded by the ABCC8 gene). Although all SUs are mechanistically similar in terms of&#xD;
      increasing insulin secretion, they bind to distinct regions of Kir 6.2 and SUR1 to exert&#xD;
      their function. Different types of SU (e.g. tolbutamide, glibenclamide, glipizide,&#xD;
      glimepiride and gliclazide) can therefore be grouped by their binding sites (A/B/A+B site) on&#xD;
      the KATP channel [3]. Interestingly, the KCNJ11 E23K (rs5219) variant was shown to confer&#xD;
      susceptibility to T2DM and the ABCC8 S1369A (rs757110) variant was found to be in complete&#xD;
      linkage disequilibrium with it i.e. inherited together as a genetic block (haplotype). A&#xD;
      recent in vitro molecular study suggested that the minor haplotype (K23/A1369) of KATP&#xD;
      channel is sensitive to inhibition by gliclazide (binds to A-site) but not glibenclamide&#xD;
      (binds to A+B site), and that the increased responsiveness to gliclazide was largely due to&#xD;
      the A1369 allele. Understanding how the response to these two SUs may vary with the presence&#xD;
      of the minor haplotype (K23/A1369) would therefore be beneficial for customization of patient&#xD;
      treatment to achieve better clinical outcomes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">July 2016</completion_date>
  <primary_completion_date type="Actual">June 2016</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean blood glucose level</measure>
    <time_frame>6 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Glycemic variability</measure>
    <time_frame>6 days</time_frame>
    <description>Glycemic variability will be assessed using the EasyGV software (http://www.phc.ox.ac.uk/research/diabetes/software/easygv/) which is capable of calculating 10 different measures of glycemic variability from continuous glucose monitoring data, such as Standard Deviation (SD) and M-value, mean amplitude of glycemic excursions (MAGE).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Diabetes</condition>
  <arm_group>
    <arm_group_label>Gliclazide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Gliclazide, 80 mg tablet, half to maximal dose, 3 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Glibenclamide</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Glibenclamide, 5 mg tablet, half to maximal dose, 3 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gliclazide</intervention_name>
    <arm_group_label>Gliclazide</arm_group_label>
    <other_name>Sun-Glizide</other_name>
    <other_name>SIN09350P</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Glibenclamide</intervention_name>
    <arm_group_label>Glibenclamide</arm_group_label>
    <other_name>Benil</other_name>
    <other_name>SIN07284P</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Type 2 diabetes&#xD;
&#xD;
          -  Age 21-65&#xD;
&#xD;
          -  HbA1c &gt;8.0% on two consecutive visits&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Currently taking insulin at a regime more complex than basal insulin&#xD;
&#xD;
          -  Not willing to perform self-blood glucose monitoring (SBGM)&#xD;
&#xD;
          -  Renal impairment i.e. eGFR&lt;50mls/min&#xD;
&#xD;
          -  Pregnancy or unwilling to practice adequate contraception&#xD;
&#xD;
          -  Taking other medications that may affect blood glucose e.g. systemic glucocorticoids.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Su Chi Lim, MBBS, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Khoo Teck Puat Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Khoo Teck Puat Hospital</name>
      <address>
        <city>Singapore</city>
        <zip>768828</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Singapore</country>
  </location_countries>
  <reference>
    <citation>Gloyn AL, Weedon MN, Owen KR, Turner MJ, Knight BA, Hitman G, Walker M, Levy JC, Sampson M, Halford S, McCarthy MI, Hattersley AT, Frayling TM. Large-scale association studies of variants in genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes. Diabetes. 2003 Feb;52(2):568-72. doi: 10.2337/diabetes.52.2.568.</citation>
    <PMID>12540637</PMID>
  </reference>
  <reference>
    <citation>Hamming KS, Soliman D, Matemisz LC, Niazi O, Lang Y, Gloyn AL, Light PE. Coexpression of the type 2 diabetes susceptibility gene variants KCNJ11 E23K and ABCC8 S1369A alter the ATP and sulfonylurea sensitivities of the ATP-sensitive K(+) channel. Diabetes. 2009 Oct;58(10):2419-24. doi: 10.2337/db09-0143. Epub 2009 Jul 8.</citation>
    <PMID>19587354</PMID>
  </reference>
  <verification_date>August 2016</verification_date>
  <study_first_submitted>July 22, 2014</study_first_submitted>
  <study_first_submitted_qc>July 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 28, 2014</study_first_posted>
  <last_update_submitted>August 31, 2016</last_update_submitted>
  <last_update_submitted_qc>August 31, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 1, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Khoo Teck Puat Hospital</investigator_affiliation>
    <investigator_full_name>Su Chi Lim</investigator_full_name>
    <investigator_title>Senior Consultant</investigator_title>
  </responsible_party>
  <keyword>sulphonylureas</keyword>
  <keyword>gliclazide</keyword>
  <keyword>glibenclamide</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gliclazide</mesh_term>
    <mesh_term>Glyburide</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02201602
org study id: Gliclazide
nct id: NCT02201602
lead sponsor: 
has dmc: No
Gliclazide has greater glucose lowering efficacy than glibenclamide among type 2 diabetes
      mellitus patients with minor haplotype (K23/A1369) at the KCNJ11/ABCC gene locations.
Sulphonylurea (SU) is a glucose-lowering agent used widely to treat type 2 diabetes mellitus
      (T2DM). SU promotes insulin secretion from the pancreatic islet beta cell via binding and
      inhibition of the ATP-sensitive potassium (KATP) channel. The KATP channel is made up of two
      subcomponents, an inner Kir6.2 K+ channel (coded by the KCNJ11 gene) and an outer SU receptor
      1 (SUR1) (coded by the ABCC8 gene). Although all SUs are mechanistically similar in terms of
      increasing insulin secretion, they bind to distinct regions of Kir 6.2 and SUR1 to exert
      their function. Different types of SU (e.g. tolbutamide, glibenclamide, glipizide,
      glimepiride and gliclazide) can therefore be grouped by their binding sites (A/B/A+B site) on
      the KATP channel [3]. Interestingly, the KCNJ11 E23K (rs5219) variant was shown to confer
      susceptibility to T2DM and the ABCC8 S1369A (rs757110) variant was found to be in complete
      linkage disequilibrium with it i.e. inherited together as a genetic block (haplotype). A
      recent in vitro molecular study suggested that the minor haplotype (K23/A1369) of KATP
      channel is sensitive to inhibition by gliclazide (binds to A-site) but not glibenclamide
      (binds to A+B site), and that the increased responsiveness to gliclazide was largely due to
      the A1369 allele. Understanding how the response to these two SUs may vary with the presence
      of the minor haplotype (K23/A1369) would therefore be beneficial for customization of patient
      treatment to achieve better clinical outcomes.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Mean blood glucose level
time frame: 6 days
measure: Glycemic variability
time frame: 6 days
description: Glycemic variability will be assessed using the EasyGV software (http://www.phc.ox.ac.uk/research/diabetes/software/easygv/) which is capable of calculating 10 different measures of glycemic variability from continuous glucose monitoring data, such as Standard Deviation (SD) and M-value, mean amplitude of glycemic excursions (MAGE).
arm group label: Gliclazide
arm group type: Experimental
description: Gliclazide, 80 mg tablet, half to maximal dose, 3 weeks
arm group label: Glibenclamide
arm group type: Active Comparator
description: Glibenclamide, 5 mg tablet, half to maximal dose, 3 weeks
intervention type: Drug
intervention name: Gliclazide
arm group label: Gliclazide
other name: Sun-Glizide
other name: SIN09350P
intervention type: Drug
intervention name: Glibenclamide
arm group label: Glibenclamide
other name: Benil
other name: SIN07284P
criteria: 
gender: All
minimum age: 21 Years
maximum age: 65 Years
healthy volunteers: No
last name: Su Chi Lim, MBBS, PhD
role: Principal Investigator
affiliation: Khoo Teck Puat Hospital
facility: 
country: Singapore
citation: Gloyn AL, Weedon MN, Owen KR, Turner MJ, Knight BA, Hitman G, Walker M, Levy JC, Sampson M, Halford S, McCarthy MI, Hattersley AT, Frayling TM. Large-scale association studies of variants in genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes. Diabetes. 2003 Feb;52(2):568-72. doi: 10.2337/diabetes.52.2.568.
PMID: 12540637
citation: Hamming KS, Soliman D, Matemisz LC, Niazi O, Lang Y, Gloyn AL, Light PE. Coexpression of the type 2 diabetes susceptibility gene variants KCNJ11 E23K and ABCC8 S1369A alter the ATP and sulfonylurea sensitivities of the ATP-sensitive K(+) channel. Diabetes. 2009 Oct;58(10):2419-24. doi: 10.2337/db09-0143. Epub 2009 Jul 8.
PMID: 19587354
responsible party type: Principal Investigator
investigator affiliation: Khoo Teck Puat Hospital
investigator full name: Su Chi Lim
investigator title: Senior Consultant
mesh term: Gliclazide
mesh term: Glyburide