<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/NCT02256189</url>
  </required_header>
  <id_info>
    <org_study_id>300A</org_study_id>
    <nct_id>NCT02256189</nct_id>
  </id_info>
  <brief_title>Sitagliptin and Glucagon Counterregulation</brief_title>
  <acronym>SITACLAMP</acronym>
  <official_title>The Effect of Sitagliptin on Glucagon Counterregulation and Incretin Hormones During Mild Hypoglycemia in Elderly Patients With Metformin-treated Type 2 Diabetes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lund University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Lund University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To evaluate the effect of DPP-4 inhibition on glucagon counter-regulatory mechanisms at&#xD;
      moderate hypoglycemia in metformin-treated subjects with T2DM&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The glucagon response to mild (3.0 mmol/l) hypoglycemia with and without DPP-4 inhibition by&#xD;
      sitagliptin will be evaluated in elderly subjects with metformin treated type 2 diabetes to&#xD;
      explore whether DPP-4 inhibition affects glucagon counter-regulation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 2015</start_date>
  <completion_date type="Actual">June 2017</completion_date>
  <primary_completion_date type="Actual">June 2017</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>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Glucagon Counterregulation to Hypoglycemia</measure>
    <time_frame>Four weeks treatment</time_frame>
    <description>Change in plasma glucagon to insulin-induced hypoglycemia after four weeks of treatment with sitagliptin and placebo</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>Type 2 Diabetes</condition>
  <arm_group>
    <arm_group_label>Sitagliptin first, then placebo</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Sitagliptin treatment for four weeks, then washout for four weeks, then placebo for four weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo first, then sitagliptin</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Placebo for four weeks, then washout for four weeks, then sitagliptin for four weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sitagliptin</intervention_name>
    <description>Sitagliptin 100 mg daily</description>
    <arm_group_label>Sitagliptin first, then placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo one tablet daily</description>
    <arm_group_label>Placebo first, then sitagliptin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Written consent has been given.&#xD;
&#xD;
          2. Patients with metformin treated T2DM (metformin dose &gt;0,5 g/day and stable during the&#xD;
             preceding 3 months)&#xD;
&#xD;
          3. Age &gt;65 years.&#xD;
&#xD;
          4. HbA1c 6.0-8.5% (43-67 mmol/mol; inclusive) at visit 1.&#xD;
&#xD;
          5. Ability to complete the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. A history of any secondary forms of diabetes, e.g., Cushing's syndrome and acromegaly.&#xD;
&#xD;
          2. Type 2 diabetes, positive GAD antibodies&#xD;
&#xD;
          3. eGFR &lt;60 ml/min&#xD;
&#xD;
          4. Acute infections which may affect blood glucose control within 4 weeks prior to visit&#xD;
             1&#xD;
&#xD;
          5. Any history of recent (&lt;2 weeks) recurrent or severe hypoglycemic episodes.&#xD;
&#xD;
          6. Liver disease such as cirrhosis or chronic active hepatitis&#xD;
&#xD;
          7. History of coronary heart disease or heart failure class III or IV&#xD;
&#xD;
          8. Donation of one unit (500 ml) or more of blood, significant blood loss equaling to at&#xD;
             least one unit of blood within the past 2 weeks or a blood transfusion within the past&#xD;
             8 weeks.&#xD;
&#xD;
          9. Treatment with growth hormone of chronic oral or parenteral corticosteroid treatment&#xD;
             (&gt; 7 consecutive days of treatment) within 8 weeks prior to visit 1.&#xD;
&#xD;
         10. Use of other investigational drugs at visit 1 or within 30 days of visit 1, unsuitable&#xD;
             for the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bo Ahrén, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Lund University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Skane University Hospital Malmö</name>
      <address>
        <city>Malmö</city>
        <zip>20502</zip>
        <country>Sweden</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Sweden</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>September 29, 2014</study_first_submitted>
  <study_first_submitted_qc>September 30, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 3, 2014</study_first_posted>
  <results_first_submitted>October 18, 2017</results_first_submitted>
  <results_first_submitted_qc>October 14, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">February 20, 2019</results_first_posted>
  <last_update_submitted>October 14, 2018</last_update_submitted>
  <last_update_submitted_qc>October 14, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 20, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Lund University</investigator_affiliation>
    <investigator_full_name>Bo Ahren</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <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>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 12, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/89/NCT02256189/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 12, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/89/NCT02256189/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Sitagliptin First, Then Placebo</title>
          <description>Sitagliptin first for four weeks, then washout for four weeks, then placebo for four weeks</description>
        </group>
        <group group_id="P2">
          <title>Placebo First, Then Sitagliptin</title>
          <description>Placebo first for four weeks, then washout for four weeks, then placebo for four weeks</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Sitagliptin First, Then Placebo</title>
          <description>Hypoglycemia clamp with sitagliptin&#xD;
Sitagliptin: Treatment with sitagliptin 100mg QD for four weeks followed by hyperinsulinemic hypoglycemic clamp</description>
        </group>
        <group group_id="B2">
          <title>Placebo First, Then Stagliptin</title>
          <description>Hypoglycemia clamp with placebo&#xD;
Placebo: Treatment with placebo QD for four weeks followed by hyperinsulinemic hypoglycemic clamp</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="15"/>
            <count group_id="B2" value="13"/>
            <count group_id="B3" value="28"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="75.0" spread="5.9"/>
                    <measurement group_id="B2" value="71.9" spread="5.7"/>
                    <measurement group_id="B3" value="73.6" spread="5.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Sweden</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Fasting glucagon</title>
          <units>pmol/l</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29.5" spread="9.7"/>
                    <measurement group_id="B2" value="30.0" spread="12.2"/>
                    <measurement group_id="B3" value="29.8" spread="10.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Glucagon Counterregulation to Hypoglycemia</title>
        <description>Change in plasma glucagon to insulin-induced hypoglycemia after four weeks of treatment with sitagliptin and placebo</description>
        <time_frame>Four weeks treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sitagliptin</title>
            <description>Hypoglycemia clamp with sitagliptin&#xD;
Sitagliptin: Treatment with sitagliptin 100mg QD for four weeks followed by hyperinsulinemic hypoglycemic clamp</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Hypoglycemia clamp with placebo&#xD;
Placebo: Treatment with placebo QD for four weeks followed by hyperinsulinemic hypoglycemic clamp</description>
          </group>
        </group_list>
        <measure>
          <title>Glucagon Counterregulation to Hypoglycemia</title>
          <description>Change in plasma glucagon to insulin-induced hypoglycemia after four weeks of treatment with sitagliptin and placebo</description>
          <units>pmol/l</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="28"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.0" spread="2.9"/>
                    <measurement group_id="O2" value="16.5" spread="2.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>4 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Sitagliptin First, Then Placebo</title>
          <description>Sitagliptin first for four weeks, then washout for four weeks, then placebo for four weeks</description>
        </group>
        <group group_id="E2">
          <title>Placebo First, Then Stagliptin</title>
          <description>Placebo first for four weeks, then washout for four weeks, then sitalgiptin for four weeks</description>
        </group>
        <group group_id="E3">
          <title>Sitagliptin</title>
          <description>Sitagliptin 100mg Daily for four weeks, either before or after a 4 week placebo period</description>
        </group>
        <group group_id="E4">
          <title>Placebo</title>
          <description>Placebo Daily for four weeks, efter before or after a 4 week sitagliptin period</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="15"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="13"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Professor Bo Ahrén</name_or_title>
      <organization>Lund University</organization>
      <phone>+46462220758</phone>
      <email>Bo.Ahren@med.lu.se</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02256189
org study id: 300A
nct id: NCT02256189
lead sponsor: 
collaborator: 
has dmc: No
To evaluate the effect of DPP-4 inhibition on glucagon counter-regulatory mechanisms at
      moderate hypoglycemia in metformin-treated subjects with T2DM
The glucagon response to mild (3.0 mmol/l) hypoglycemia with and without DPP-4 inhibition by
      sitagliptin will be evaluated in elderly subjects with metformin treated type 2 diabetes to
      explore whether DPP-4 inhibition affects glucagon counter-regulation.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Glucagon Counterregulation to Hypoglycemia
time frame: Four weeks treatment
description: Change in plasma glucagon to insulin-induced hypoglycemia after four weeks of treatment with sitagliptin and placebo
arm group label: Sitagliptin first, then placebo
arm group type: Other
description: Sitagliptin treatment for four weeks, then washout for four weeks, then placebo for four weeks
arm group label: Placebo first, then sitagliptin
arm group type: Other
description: Placebo for four weeks, then washout for four weeks, then sitagliptin for four weeks
intervention type: Drug
intervention name: Sitagliptin
description: Sitagliptin 100 mg daily
arm group label: Sitagliptin first, then placebo
intervention type: Drug
intervention name: Placebo
description: Placebo one tablet daily
arm group label: Placebo first, then sitagliptin
criteria: 
gender: All
minimum age: 65 Years
maximum age: 90 Years
healthy volunteers: No
last name: Bo Ahrén, MD, PhD
role: Principal Investigator
affiliation: Lund University
facility: 
country: Sweden
responsible party type: Principal Investigator
investigator affiliation: Lund University
investigator full name: Bo Ahren
investigator title: Professor
mesh term: Diabetes Mellitus, Type 2
mesh term: Sitagliptin Phosphate
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 