<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/NCT01660386</url>
  </required_header>
  <id_info>
    <org_study_id>CCEMD014</org_study_id>
    <nct_id>NCT01660386</nct_id>
  </id_info>
  <brief_title>Study of Comparing the Different Effect of DPP-4 Inhibitors and Sulfonylurea by Using &quot;Biphase-Hyperglycemic Clamp&quot;</brief_title>
  <official_title>An Open-label, Randomized, Four-way Cross-over, Single Dose Study to Compare the Different Effect of DPP-4 Inhibitors and Sulfonylurea on the Beta Cell Function by Using &quot;Biphase-Hyperglycemic Clamp&quot;</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Jiao Tong University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shanghai Jiao Tong University School of Medicine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this study is to demonstrate the different effects of two DPP-4&#xD;
      inhibitors(Sitagliptin, Saxagliptin)and the insulin secretagogue: glimepiride on first and&#xD;
      second phase insulin secretion by using a Biphase-Hyperglycemic Clamp and to explore the&#xD;
      different effects of the study drugs on the GLP-1 response, and the glucagon concentration&#xD;
      which indicates alpha cell function in healthy subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      After enrollment and two weeks screening period eligible subjects will be counseled to follow&#xD;
      a dietary program for approximately 2 wk and recorded of personal history, full clinical&#xD;
      examination and screening blood samples.&#xD;
&#xD;
      Subjects will be randomized using a computer-generated allocation schedule to one of 12&#xD;
      sequences during which each subjects will be assigned to take 4 times of bi-phase&#xD;
      hyperglycaemic clamp experiments at a randomized sequence separated by a washout period of&#xD;
      7-14d.&#xD;
&#xD;
      At each experimental day, the subject will take the given dose of Sitagliptin, Saxagliptin,&#xD;
      Glimepiride and nothing for blank control two hours before the clamp experiment starts.&#xD;
&#xD;
      The hyperglycaemic clamp will be performed after an overnight fast. Subjects will be placed&#xD;
      in a recumbent position and cannula will be inserted in a dorsal hand vein. The hand will be&#xD;
      placed in a heating box (42C) throughout the experiment to allow frequent sampling of&#xD;
      arterialized blood. A second cannula will be inserted in a contralateral cubital vein for&#xD;
      glucose infusion.&#xD;
&#xD;
      At time zero (0 min), a 50% glucose bolus will be injected during 1 min to increase PG to&#xD;
      12mM. The glucose bolus will be calculated as:(12mM-FPG)×35 mg glucose × body weight (kg). PG&#xD;
      will be measured bedside every 5 min and maintained at 12mM by an adjustable continuous 20%&#xD;
      glucose infusion. After 90min, PG will be lowered down below 6mM for the islet cells to rest,&#xD;
      then the subject will be instructed to consume 75g glucose solution orally in 5min, PG will&#xD;
      be measured bedside every 5 min and maintained below 6mM for 40min then restart the&#xD;
      90min-hyperglycaemic clamp experiment. The oral period of hyperglycaemic clamp process is the&#xD;
      same as what's done in fasting period. Blood samples will be collected in -2h, 0min, 10min,&#xD;
      90min in both hyperglycaemic clamp experimental process for the measurement of insulin,&#xD;
      C-peptide, glucagon, active GLP-1, total GLP-1 and DPP-4 activity.&#xD;
&#xD;
      Thus we could evaluate the beta cell function represented by the first phase and the second&#xD;
      phase of insulin secretion(C-peptide secretion) and alpha cell function represented by the&#xD;
      change of glucagon concentration during the fasting period and oral period of hyperglycaemic&#xD;
      clamp experiment and the change of active GLP-1, total GLP-1 and DPP-4 activity as well.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>July 2012</start_date>
  <completion_date type="Anticipated">March 2013</completion_date>
  <primary_completion_date type="Anticipated">December 2012</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>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The acute phase and second phase of insulin secretion and C peptide secretion</measure>
    <time_frame>1-2 months</time_frame>
    <description>The primary outcome measures are improvement in beta cell function measured as insulin secretion and C-peptide secretion during the bi-phase hyperglycaemic clamp. The first phase of insulin and C-peptide secretion is defined as the secretion between 0-10min, the second phase is defined as secretion between 20-90min of bi-phase hyperglycaemic clamp</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Alpha cell function,GLP-1 response</measure>
    <time_frame>1-2 months</time_frame>
    <description>The secondary outcome measures are a relative increase in glucagon concentration which indicates alpha cell function and the GLP-1 response, DPP-4 activity and before taken the medicine and in 0, 10, 90,150,160,240min during the bi-phase hyperglycaemic clamp.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">12</enrollment>
  <condition>Type 2 Diabetes</condition>
  <arm_group>
    <arm_group_label>Sitagliptin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>the subjects are asked to take one pill of sitagliptin(100mg po once) in 7am of experimental day then start bi-phase hyperglycaemic clamp at 9am.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Saxagliptin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>the subjects are asked to take one pill of saxagliptin(5mg po once) in 7am of experimental day then start bi-phase hyperglycaemic clamp at 9am.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Glimepiride</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>the subjects are asked to take one pill of glimepiride(2mg po once) in 7am of experimental day then start bi-phase hyperglycaemic clamp at 9am.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Blank control</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>the subjects take no medication at experimental day and start bi-phase hyperglycaemic clamp at 9am.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sitagliptin</intervention_name>
    <description>100mg po once</description>
    <arm_group_label>Sitagliptin</arm_group_label>
    <other_name>Januvia</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Saxagliptin</intervention_name>
    <description>5mg po once</description>
    <arm_group_label>Saxagliptin</arm_group_label>
    <other_name>Onglyza</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Glimepiride</intervention_name>
    <description>2mg po once</description>
    <arm_group_label>Glimepiride</arm_group_label>
    <other_name>Amaryl</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Blank control</intervention_name>
    <description>the subjects take no medication at experimental day and start bi-phase hyperglycaemic clamp at 9am.</description>
    <arm_group_label>Blank control</arm_group_label>
    <other_name>Baseline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Understand and voluntarily sign an informed consent document prior to any study&#xD;
             related assessments/procedures are conducted;&#xD;
&#xD;
          2. Having good study compliance;&#xD;
&#xD;
          3. Healthy Male subjects between 20-30 years of age (inclusive), and in good health as&#xD;
             determined by past medical history, physical examination, vital signs, and clinical&#xD;
             laboratory test;&#xD;
&#xD;
          4. Must have a body mass index (BMI) between 19-25kg/m2 (inclusive);&#xD;
&#xD;
          5. No weight fluctuation greater than 5% in late 3 months。&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. With impaired glucose tolerance, T2DM or any significant medical condition (within 3&#xD;
             years), laboratory abnormality, or psychiatric illness that would prevent the subject&#xD;
             from participating in the study;&#xD;
&#xD;
          2. Used any prescribed systemic or topical medication within 30 days of the first dose&#xD;
             administration;&#xD;
&#xD;
          3. Any medical or surgical conditions possibly affecting study drug absorption,&#xD;
             distribution, metabolism and excretion;&#xD;
&#xD;
          4. Participated in a clinical study involving administration of an investigational drug&#xD;
             within 90 days preceding the first dose administration or within five half-lives of&#xD;
             the first dose administration (whichever is longer);&#xD;
&#xD;
          5. Donated blood or plasma or had any other significant blood loss within 2 months&#xD;
             preceding the first dose administration;&#xD;
&#xD;
          6. History of multiple drug allergies;&#xD;
&#xD;
          7. Any clinically significant allergic disease;&#xD;
&#xD;
          8. Recently drug or alcohol abuse (&gt;35 unit/week, 1 unit=8g alcohol @ 1 standard drink @&#xD;
             250ml beer @ 140ml wine @ 25ml strong alcohol drink like whiskey);&#xD;
&#xD;
          9. Smokers or users of other tobacco products in the 3 months prior to screening.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>30 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Guang Ning, MD. PHD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shanghai Jiao Tong University School of Medicine</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Guang Ning, MD. PHD</last_name>
    <phone>+8621-64370045</phone>
    <phone_ext>665340</phone_ext>
    <email>guangning@medmail.com.cn</email>
  </overall_contact>
  <location>
    <facility>
      <name>Shanghai Jiao Tong University School of Medicine</name>
      <address>
        <city>Shanghai</city>
        <zip>200021</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Guang Ning, MD,PHD</last_name>
      <phone>+8621-64370045</phone>
      <phone_ext>665340</phone_ext>
      <email>guangning@medmail.com.cn</email>
    </contact>
    <investigator>
      <last_name>Guang Ning, MD,PHD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>December 2012</verification_date>
  <study_first_submitted>August 5, 2012</study_first_submitted>
  <study_first_submitted_qc>August 5, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 8, 2012</study_first_posted>
  <last_update_submitted>December 13, 2012</last_update_submitted>
  <last_update_submitted_qc>December 13, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 17, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Shanghai Jiao Tong University School of Medicine</investigator_affiliation>
    <investigator_full_name>Guang Ning</investigator_full_name>
    <investigator_title>the vice-president of Shanghai Jiao Tong University affiliated Rui jin Hospital</investigator_title>
  </responsible_party>
  <keyword>Type 2 Diabetes</keyword>
  <keyword>Dpp-4 inhibitor</keyword>
  <keyword>Sulfonylurea</keyword>
  <keyword>beta cell function</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sitagliptin Phosphate</mesh_term>
    <mesh_term>Glimepiride</mesh_term>
    <mesh_term>Saxagliptin</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>March 18, 2013</submitted>
    <returned>May 1, 2013</returned>
    <submitted>May 3, 2013</submitted>
    <returned>June 7, 2013</returned>
    <submitted>June 17, 2013</submitted>
    <submission_canceled>Unknown</submission_canceled>
    <submitted>June 18, 2013</submitted>
    <submission_canceled>Unknown</submission_canceled>
  </pending_results>
  <!-- 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/NCT01660386
org study id: CCEMD014
nct id: NCT01660386
lead sponsor: 
has dmc: Yes
The objective of this study is to demonstrate the different effects of two DPP-4
      inhibitors(Sitagliptin, Saxagliptin)and the insulin secretagogue: glimepiride on first and
      second phase insulin secretion by using a Biphase-Hyperglycemic Clamp and to explore the
      different effects of the study drugs on the GLP-1 response, and the glucagon concentration
      which indicates alpha cell function in healthy subjects.
After enrollment and two weeks screening period eligible subjects will be counseled to follow
      a dietary program for approximately 2 wk and recorded of personal history, full clinical
      examination and screening blood samples.

      Subjects will be randomized using a computer-generated allocation schedule to one of 12
      sequences during which each subjects will be assigned to take 4 times of bi-phase
      hyperglycaemic clamp experiments at a randomized sequence separated by a washout period of
      7-14d.

      At each experimental day, the subject will take the given dose of Sitagliptin, Saxagliptin,
      Glimepiride and nothing for blank control two hours before the clamp experiment starts.

      The hyperglycaemic clamp will be performed after an overnight fast. Subjects will be placed
      in a recumbent position and cannula will be inserted in a dorsal hand vein. The hand will be
      placed in a heating box (42C) throughout the experiment to allow frequent sampling of
      arterialized blood. A second cannula will be inserted in a contralateral cubital vein for
      glucose infusion.

      At time zero (0 min), a 50% glucose bolus will be injected during 1 min to increase PG to
      12mM. The glucose bolus will be calculated as:(12mM-FPG)×35 mg glucose × body weight (kg). PG
      will be measured bedside every 5 min and maintained at 12mM by an adjustable continuous 20%
      glucose infusion. After 90min, PG will be lowered down below 6mM for the islet cells to rest,
      then the subject will be instructed to consume 75g glucose solution orally in 5min, PG will
      be measured bedside every 5 min and maintained below 6mM for 40min then restart the
      90min-hyperglycaemic clamp experiment. The oral period of hyperglycaemic clamp process is the
      same as what's done in fasting period. Blood samples will be collected in -2h, 0min, 10min,
      90min in both hyperglycaemic clamp experimental process for the measurement of insulin,
      C-peptide, glucagon, active GLP-1, total GLP-1 and DPP-4 activity.

      Thus we could evaluate the beta cell function represented by the first phase and the second
      phase of insulin secretion(C-peptide secretion) and alpha cell function represented by the
      change of glucagon concentration during the fasting period and oral period of hyperglycaemic
      clamp experiment and the change of active GLP-1, total GLP-1 and DPP-4 activity as well.
allocation: Randomized
intervention model: Crossover Assignment
masking: None (Open Label)
measure: The acute phase and second phase of insulin secretion and C peptide secretion
time frame: 1-2 months
description: The primary outcome measures are improvement in beta cell function measured as insulin secretion and C-peptide secretion during the bi-phase hyperglycaemic clamp. The first phase of insulin and C-peptide secretion is defined as the secretion between 0-10min, the second phase is defined as secretion between 20-90min of bi-phase hyperglycaemic clamp
measure: Alpha cell function,GLP-1 response
time frame: 1-2 months
description: The secondary outcome measures are a relative increase in glucagon concentration which indicates alpha cell function and the GLP-1 response, DPP-4 activity and before taken the medicine and in 0, 10, 90,150,160,240min during the bi-phase hyperglycaemic clamp.
arm group label: Sitagliptin
arm group type: Experimental
description: the subjects are asked to take one pill of sitagliptin(100mg po once) in 7am of experimental day then start bi-phase hyperglycaemic clamp at 9am.
arm group label: Saxagliptin
arm group type: Experimental
description: the subjects are asked to take one pill of saxagliptin(5mg po once) in 7am of experimental day then start bi-phase hyperglycaemic clamp at 9am.
arm group label: Glimepiride
arm group type: Experimental
description: the subjects are asked to take one pill of glimepiride(2mg po once) in 7am of experimental day then start bi-phase hyperglycaemic clamp at 9am.
arm group label: Blank control
arm group type: Other
description: the subjects take no medication at experimental day and start bi-phase hyperglycaemic clamp at 9am.
intervention type: Drug
intervention name: Sitagliptin
description: 100mg po once
arm group label: Sitagliptin
other name: Januvia
intervention type: Drug
intervention name: Saxagliptin
description: 5mg po once
arm group label: Saxagliptin
other name: Onglyza
intervention type: Drug
intervention name: Glimepiride
description: 2mg po once
arm group label: Glimepiride
other name: Amaryl
intervention type: Drug
intervention name: Blank control
description: the subjects take no medication at experimental day and start bi-phase hyperglycaemic clamp at 9am.
arm group label: Blank control
other name: Baseline
criteria: 
gender: Male
minimum age: 20 Years
maximum age: 30 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Guang Ning, MD. PHD
role: Principal Investigator
affiliation: Shanghai Jiao Tong University School of Medicine
last name: Guang Ning, MD. PHD
phone: +8621-64370045
phone ext: 665340
email: guangning@medmail.com.cn
facility: 
status: Recruiting
contact: 
investigator: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Shanghai Jiao Tong University School of Medicine
investigator full name: Guang Ning
investigator title: the vice-president of Shanghai Jiao Tong University affiliated Rui jin Hospital
mesh term: Diabetes Mellitus, Type 2
mesh term: Sitagliptin Phosphate
mesh term: Glimepiride
mesh term: Saxagliptin
submitted: March 18, 2013
returned: May 1, 2013
submitted: May 3, 2013
returned: June 7, 2013
submitted: June 17, 2013
submission canceled: Unknown
submitted: June 18, 2013
submission canceled: Unknown