<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/NCT02971631</url>
  </required_header>
  <id_info>
    <org_study_id>A094265</org_study_id>
    <secondary_id>218762</secondary_id>
    <nct_id>NCT02971631</nct_id>
  </id_info>
  <brief_title>Gastrectomy, Eating Behaviour and GLP-1</brief_title>
  <official_title>The Effect of Glucagon Like Peptide-1 (GLP-1) on Glycaemic Profile and Eating Behaviour Following Gastrectomy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cambridge University Hospitals NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cambridge University Hospitals NHS Foundation Trust</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients who have undergone gastrectomy (removal of the stomach) to treat or prevent cancer&#xD;
      are known to have a significantly reduced quality of life. To date, there is very little&#xD;
      information on the physiological causes of this. The investigators suspect that&#xD;
      overproduction of a hormone (chemical) called glucagon like peptide-1 (GLP-1) released by the&#xD;
      lining of the gut may play a role in the reduced appetite, weight loss and low blood sugar&#xD;
      symptoms seen in this group. To investigate this, the investigators will study the response&#xD;
      of 16 patients who have previously had a gastrectomy to a glucose drink, and a meal, while&#xD;
      receiving an infusion of a specific blocker of GLP-1 or placebo. The investigators will&#xD;
      examine the levels of sugar and associated hormones in the blood, food consumption and food&#xD;
      reward behaviour using standard tools.&#xD;
&#xD;
      Participants will be invited to attend the Clinical Research Facility at Addenbrooke's&#xD;
      Hospital for a screening visit, and two whole day study visits. The study has been designed&#xD;
      to assess the role of overproduction of GLP-1 by completely blocking its actions, rather than&#xD;
      assess the use of the blocking compound as a medication, and is therefore regarded as a&#xD;
      physiological study, not a clinical trial.&#xD;
&#xD;
      The goal of this study is to demonstrate the magnitude of effect of GLP-1 on blood sugar and&#xD;
      appetite derangement in patients who have had a gastrectomy. This will guide future work on&#xD;
      the development of novel treatment paradigms for the post-gastrectomy patient group.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 10, 2017</start_date>
  <completion_date type="Actual">September 16, 2018</completion_date>
  <primary_completion_date type="Actual">September 16, 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Nadir Blood Glucose</measure>
    <time_frame>As assessed during a 50g glucose tolerance test while receiving infusion of GLP-1 antagonist. At time 30-120 minutes of infusion of Exendin 9-39.</time_frame>
    <description>Lowest blood sugar reading during an oral glucose tolerance test while receiving infusion of GLP-1 antagonist. Please note participants will receive infusion of active compound for a maximum of four hours, with no expected effect of compound persisting for more than 30 minutes post-infusion.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Total Insulin Secretion</measure>
    <time_frame>Samples collected at 0, 15, 30, 45 and 60 minutes post oral glucose tolerance test.</time_frame>
    <description>60 minute incremental area under the curve (i.e. total) insulin secretion during 50g oral glucose tolerance test while receiving infusion of GLP-1 antagonist. Please note participants will receive infusion of active compound for a maximum of four hours, with no expected effect of compound persisting for more than 30 minutes post-infusion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Eating Rate During ad Libitum Meal</measure>
    <time_frame>150-210 minutes during infusion of Exendin 9-39 or placebo.</time_frame>
    <description>As measured by universal eating monitor, total weight of a standardised meal consumed over a measured time in grams per minute.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Decreased Hunger and Satiety Ratings During and After ad Libitum Meal</measure>
    <time_frame>150-240 minutes during infusion of Exendin 9-39 or placebo and for 4 hours post-cessation of infusion.</time_frame>
    <description>Will be measured on visual analogue scale and reported as a score out of 100. Higher value indicated more hunger and more satiety.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Altered Food Attention.</measure>
    <time_frame>0-240 minutes during infusion of Exendin 9-39 or placebo, assessed on four occasions (baseline or T0, post-OGTT, pre-meal, post-meal) using a validated dot-probe visual response tool and reported in response time (milliseconds).</time_frame>
    <description>Food motivation can be measured by response rates to visual cues while being distracted by food related images. Will be measured with and without GLP-1 blockade to investigate effects of GLP-1 on food attention behaviour. Measure is of difference in response time when visual cue is colocated with a food related image vs a non-food related image, indicating degree of bias in attention to food images. Measure is undertaken during infusion at four timepoints - baseline (i.e. fasting), post oral glucose tolerance test (post-OGTT), before a standard meal (pre-meal) and after the meal (post-meal).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Altered Food Motivation</measure>
    <time_frame>0-240 minutes during infusion of Exendin 9-39 or placebo (baseline or T0, post-OGTT, pre-m, assessed on four occasions using a validated grip strength surrogate of food motivation and measured as the area under the curve of a grip force monitoring curve.</time_frame>
    <description>Participant motivation to view particular food based cues is assessed by grip strength exerted to maintain those cues. Measure is undertaken during infusion at four timepoints - baseline (i.e. fasting), post oral glucose tolerance test (post-OGTT), before a standard meal (pre-meal) and after the meal (post-meal).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Infusion Related Adverse Events as Assessed by CTCAE v4</measure>
    <time_frame>24 hours from onset of infusion.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Meal Consumption</measure>
    <time_frame>150-210 minutes during infusion of Exendin 9-39 or placebo</time_frame>
    <description>Total consumption amount of a standard meal during study intervention, measured in grams using a universal eating monitor.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Gastric Cancer</condition>
  <condition>Dumping Syndrome</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Infusion of 1% human albumin in normal saline.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Exendin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Infusion of Exendin 9-39 in 1% human albumin in normal saline</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Exendin 9-39</intervention_name>
    <description>Complete blockade of action of endogenous GLP-1 by Exendin 9-39. Defined as a physiological study, not a clinical trial as such (as advised by the UK MHRA).</description>
    <arm_group_label>Exendin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Infusion of 1% human albumin in normal saline</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  • At least 3 months post completion of treatment for gastric cancer, or prophylactic&#xD;
             gastrectomy&#xD;
&#xD;
               -  Aged at least 18 years&#xD;
&#xD;
               -  Able to tolerate an oral glucose tolerance test&#xD;
&#xD;
               -  Able to understand and retain all information regarding the study and give&#xD;
                  informed consent.&#xD;
&#xD;
               -  Willing to receive an infusion of human albumin solution&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  • Have a diagnosis of diabetes&#xD;
&#xD;
               -  Have a history of untreated anaemia in the last 3 months&#xD;
&#xD;
               -  Be aged under 18 years&#xD;
&#xD;
               -  Have active gastric cancer&#xD;
&#xD;
               -  Be pregnant or attempting to conceive&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Geoffrey Roberts, MA BM BCh</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Cambridge</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cambridge University Hospitals NHS Foundation Trust</name>
      <address>
        <city>Cambridge</city>
        <state>Cambridgeshire</state>
        <zip>CB2 0QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>August 2019</verification_date>
  <study_first_submitted>November 17, 2016</study_first_submitted>
  <study_first_submitted_qc>November 20, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 23, 2016</study_first_posted>
  <results_first_submitted>September 17, 2018</results_first_submitted>
  <results_first_submitted_qc>August 27, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">August 29, 2019</results_first_posted>
  <last_update_submitted>August 27, 2019</last_update_submitted>
  <last_update_submitted_qc>August 27, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">August 29, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Cambridge University Hospitals NHS Foundation Trust</investigator_affiliation>
    <investigator_full_name>Geoffrey Roberts</investigator_full_name>
    <investigator_title>Clinical Research Associate</investigator_title>
  </responsible_party>
  <keyword>Dumping syndrome</keyword>
  <keyword>Gastrectomy</keyword>
  <keyword>GLP-1</keyword>
  <keyword>Insulin</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dumping Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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>November 24, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/31/NCT02971631/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Five participants recruited from Hereditary Diffuse Gastric Cancer patient population</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo Then Exendin</title>
          <description>Infusion of 1% human albumin in normal saline on day one of study. Infusion of Exendin 9-39 in 1% human albumin in normal saline on day two of study (bolus of 7500pmol/kg followed by infusion of 500pmol/kg/minute for 4 hours).</description>
        </group>
        <group group_id="P2">
          <title>Exendin Then Placebo</title>
          <description>Infusion of Exendin 9-39 in 1% human albumin in normal saline on day one of study (bolus of 7500pmol/kg followed by infusion of 500pmol/kg/minute for 4 hours).&#xD;
Infusion of 1% human albumin in normal saline on day two of study.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>First Intervention - One Day</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
              </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>
          <title>Second Intervention - One Day</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
              </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>All Participants</title>
          <description>All participants were randomised to reveal both interventions, so baseline characteristics are reported for the whole study population.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="5"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United Kingdom</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Nadir Blood Glucose</title>
        <description>Lowest blood sugar reading during an oral glucose tolerance test while receiving infusion of GLP-1 antagonist. Please note participants will receive infusion of active compound for a maximum of four hours, with no expected effect of compound persisting for more than 30 minutes post-infusion.</description>
        <time_frame>As assessed during a 50g glucose tolerance test while receiving infusion of GLP-1 antagonist. At time 30-120 minutes of infusion of Exendin 9-39.</time_frame>
        <population>Crossover study - analysis by paired T test</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Infusion of 1% human albumin in normal saline.&#xD;
Placebo: Infusion of 1% human albumin in normal saline</description>
          </group>
          <group group_id="O2">
            <title>Exendin</title>
            <description>Infusion of Exendin 9-39 in 1% human albumin in normal saline&#xD;
Exendin 9-39: Complete blockade of action of endogenous GLP-1 by Exendin 9-39.</description>
          </group>
        </group_list>
        <measure>
          <title>Nadir Blood Glucose</title>
          <description>Lowest blood sugar reading during an oral glucose tolerance test while receiving infusion of GLP-1 antagonist. Please note participants will receive infusion of active compound for a maximum of four hours, with no expected effect of compound persisting for more than 30 minutes post-infusion.</description>
          <population>Crossover study - analysis by paired T test</population>
          <units>mmol/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="5"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3" spread="0.3"/>
                    <measurement group_id="O2" value="4.4" spread="0.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.008</p_value>
            <method>t-test, 2 sided</method>
            <method_desc>Paired analysis</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Insulin Secretion</title>
        <description>60 minute incremental area under the curve (i.e. total) insulin secretion during 50g oral glucose tolerance test while receiving infusion of GLP-1 antagonist. Please note participants will receive infusion of active compound for a maximum of four hours, with no expected effect of compound persisting for more than 30 minutes post-infusion.</description>
        <time_frame>Samples collected at 0, 15, 30, 45 and 60 minutes post oral glucose tolerance test.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Infusion of 1% human albumin in normal saline.&#xD;
Placebo: Infusion of 1% human albumin in normal saline</description>
          </group>
          <group group_id="O2">
            <title>Exendin</title>
            <description>Infusion of Exendin 9-39 in 1% human albumin in normal saline&#xD;
Exendin 9-39: Complete blockade of action of endogenous GLP-1 by Exendin 9-39. Defined as a physiological study, not a clinical trial as such (as advised by the UK MHRA).</description>
          </group>
        </group_list>
        <measure>
          <title>Total Insulin Secretion</title>
          <description>60 minute incremental area under the curve (i.e. total) insulin secretion during 50g oral glucose tolerance test while receiving infusion of GLP-1 antagonist. Please note participants will receive infusion of active compound for a maximum of four hours, with no expected effect of compound persisting for more than 30 minutes post-infusion.</description>
          <units>pmol*minute/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="5"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41000" spread="10400"/>
                    <measurement group_id="O2" value="14500" spread="2600"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.03</p_value>
            <method>t-test, 2 sided</method>
            <method_desc>Paired analysis</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Eating Rate During ad Libitum Meal</title>
        <description>As measured by universal eating monitor, total weight of a standardised meal consumed over a measured time in grams per minute.</description>
        <time_frame>150-210 minutes during infusion of Exendin 9-39 or placebo.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Infusion of 1% human albumin in normal saline.&#xD;
Placebo: Infusion of 1% human albumin in normal saline</description>
          </group>
          <group group_id="O2">
            <title>Exendin</title>
            <description>Infusion of Exendin 9-39 in 1% human albumin in normal saline&#xD;
Exendin 9-39: Complete blockade of action of endogenous GLP-1 by Exendin 9-39. Defined as a physiological study, not a clinical trial as such (as advised by the UK MHRA).</description>
          </group>
        </group_list>
        <measure>
          <title>Eating Rate During ad Libitum Meal</title>
          <description>As measured by universal eating monitor, total weight of a standardised meal consumed over a measured time in grams per minute.</description>
          <units>grams/minute</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.62" spread="0.12"/>
                    <measurement group_id="O2" value="0.66" spread="0.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>For meal consumption rate</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.79</p_value>
            <method>t-test, 2 sided</method>
            <method_desc>Paired analysis</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Decreased Hunger and Satiety Ratings During and After ad Libitum Meal</title>
        <description>Will be measured on visual analogue scale and reported as a score out of 100. Higher value indicated more hunger and more satiety.</description>
        <time_frame>150-240 minutes during infusion of Exendin 9-39 or placebo and for 4 hours post-cessation of infusion.</time_frame>
        <population>Unfortunately it proved impossible to collect data on hunger and fullness during the ad libitum meal, due to the cognitive effects of the gastrectomy which all of this group had undergone, meaning participants were unwilling to accurately record these sensations while eating. This data is therefore meaningless and was not analysed.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Infusion of 1% human albumin in normal saline.&#xD;
Placebo: Infusion of 1% human albumin in normal saline</description>
          </group>
          <group group_id="O2">
            <title>Exendin</title>
            <description>Infusion of Exendin 9-39 in 1% human albumin in normal saline&#xD;
Exendin 9-39: Complete blockade of action of endogenous GLP-1 by Exendin 9-39.</description>
          </group>
        </group_list>
        <measure>
          <title>Decreased Hunger and Satiety Ratings During and After ad Libitum Meal</title>
          <description>Will be measured on visual analogue scale and reported as a score out of 100. Higher value indicated more hunger and more satiety.</description>
          <population>Unfortunately it proved impossible to collect data on hunger and fullness during the ad libitum meal, due to the cognitive effects of the gastrectomy which all of this group had undergone, meaning participants were unwilling to accurately record these sensations while eating. This data is therefore meaningless and was not analysed.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Altered Food Attention.</title>
        <description>Food motivation can be measured by response rates to visual cues while being distracted by food related images. Will be measured with and without GLP-1 blockade to investigate effects of GLP-1 on food attention behaviour. Measure is of difference in response time when visual cue is colocated with a food related image vs a non-food related image, indicating degree of bias in attention to food images. Measure is undertaken during infusion at four timepoints - baseline (i.e. fasting), post oral glucose tolerance test (post-OGTT), before a standard meal (pre-meal) and after the meal (post-meal).</description>
        <time_frame>0-240 minutes during infusion of Exendin 9-39 or placebo, assessed on four occasions (baseline or T0, post-OGTT, pre-meal, post-meal) using a validated dot-probe visual response tool and reported in response time (milliseconds).</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Infusion of 1% human albumin in normal saline.&#xD;
Placebo: Infusion of 1% human albumin in normal saline</description>
          </group>
          <group group_id="O2">
            <title>Exendin</title>
            <description>Infusion of Exendin 9-39 in 1% human albumin in normal saline&#xD;
Exendin 9-39: Complete blockade of action of endogenous GLP-1 by Exendin 9-39. Defined as a physiological study, not a clinical trial as such (as advised by the UK MHRA).</description>
          </group>
        </group_list>
        <measure>
          <title>Altered Food Attention.</title>
          <description>Food motivation can be measured by response rates to visual cues while being distracted by food related images. Will be measured with and without GLP-1 blockade to investigate effects of GLP-1 on food attention behaviour. Measure is of difference in response time when visual cue is colocated with a food related image vs a non-food related image, indicating degree of bias in attention to food images. Measure is undertaken during infusion at four timepoints - baseline (i.e. fasting), post oral glucose tolerance test (post-OGTT), before a standard meal (pre-meal) and after the meal (post-meal).</description>
          <units>milliseconds</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Time 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.9" spread="8.6"/>
                    <measurement group_id="O2" value="11.1" spread="7.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post OGTT</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.2" spread="4.1"/>
                    <measurement group_id="O2" value="12.0" spread="9.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-meal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.8" spread="10.8"/>
                    <measurement group_id="O2" value="17.9" spread="8.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post-meal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.7" spread="10.8"/>
                    <measurement group_id="O2" value="10.7" spread="3.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Baseline</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.20</p_value>
            <method>t-test, 2 sided</method>
            <method_desc>Paired analysis</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Post-OGTT</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.58</p_value>
            <method>t-test, 2 sided</method>
            <method_desc>Paired analysis</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Pre-meal</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.39</p_value>
            <method>t-test, 2 sided</method>
            <method_desc>Paired analysis</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Post-meal</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.20</p_value>
            <method>t-test, 2 sided</method>
            <method_desc>Paired analysis</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Altered Food Motivation</title>
        <description>Participant motivation to view particular food based cues is assessed by grip strength exerted to maintain those cues. Measure is undertaken during infusion at four timepoints - baseline (i.e. fasting), post oral glucose tolerance test (post-OGTT), before a standard meal (pre-meal) and after the meal (post-meal).</description>
        <time_frame>0-240 minutes during infusion of Exendin 9-39 or placebo (baseline or T0, post-OGTT, pre-m, assessed on four occasions using a validated grip strength surrogate of food motivation and measured as the area under the curve of a grip force monitoring curve.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Infusion of 1% human albumin in normal saline.&#xD;
Placebo: Infusion of 1% human albumin in normal saline</description>
          </group>
          <group group_id="O2">
            <title>Exendin</title>
            <description>Infusion of Exendin 9-39 in 1% human albumin in normal saline&#xD;
Exendin 9-39: Complete blockade of action of endogenous GLP-1 by Exendin 9-39. Defined as a physiological study, not a clinical trial as such (as advised by the UK MHRA).</description>
          </group>
        </group_list>
        <measure>
          <title>Altered Food Motivation</title>
          <description>Participant motivation to view particular food based cues is assessed by grip strength exerted to maintain those cues. Measure is undertaken during infusion at four timepoints - baseline (i.e. fasting), post oral glucose tolerance test (post-OGTT), before a standard meal (pre-meal) and after the meal (post-meal).</description>
          <units>Newton seconds</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>T0 / Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="508" spread="182"/>
                    <measurement group_id="O2" value="219" spread="69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post-OGTT</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="139" spread="63"/>
                    <measurement group_id="O2" value="274" spread="56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pre-meal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="328" spread="82"/>
                    <measurement group_id="O2" value="339" spread="116"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Post-meal</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="207" spread="82"/>
                    <measurement group_id="O2" value="227" spread="116"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Baseline</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.26</p_value>
            <method>t-test, 2 sided</method>
            <method_desc>Paired analysis</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Post-OGTT</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.06</p_value>
            <p_value_desc>Paired analysis</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Pre-meal</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.95</p_value>
            <method>t-test, 2 sided</method>
            <method_desc>Paired analysis</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Post-meal</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.88</p_value>
            <method>t-test, 2 sided</method>
            <method_desc>Paired analysis</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Infusion Related Adverse Events as Assessed by CTCAE v4</title>
        <time_frame>24 hours from onset of infusion.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Infusion of 1% human albumin in normal saline.&#xD;
Placebo: Infusion of 1% human albumin in normal saline</description>
          </group>
          <group group_id="O2">
            <title>Exendin</title>
            <description>Infusion of Exendin 9-39 in 1% human albumin in normal saline&#xD;
Exendin 9-39: Complete blockade of action of endogenous GLP-1 by Exendin 9-39.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Infusion Related Adverse Events as Assessed by CTCAE v4</title>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>1</p_value>
            <method>Other</method>
            <method_desc>0 events over whole study, no statistical test appropriate</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Meal Consumption</title>
        <description>Total consumption amount of a standard meal during study intervention, measured in grams using a universal eating monitor.</description>
        <time_frame>150-210 minutes during infusion of Exendin 9-39 or placebo</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Infusion of 1% human albumin in normal saline.&#xD;
Placebo: Infusion of 1% human albumin in normal saline</description>
          </group>
          <group group_id="O2">
            <title>Exendin</title>
            <description>Infusion of Exendin 9-39 in 1% human albumin in normal saline&#xD;
Exendin 9-39: Complete blockade of action of endogenous GLP-1 by Exendin 9-39. Defined as a physiological study, not a clinical trial as such (as advised by the UK MHRA).</description>
          </group>
        </group_list>
        <measure>
          <title>Total Meal Consumption</title>
          <description>Total consumption amount of a standard meal during study intervention, measured in grams using a universal eating monitor.</description>
          <units>grams</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="422" spread="45"/>
                    <measurement group_id="O2" value="434" spread="162"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.84</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>1 week.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>Infusion of 1% human albumin in normal saline.&#xD;
Placebo: Infusion of 1% human albumin in normal saline</description>
        </group>
        <group group_id="E2">
          <title>Exendin</title>
          <description>Infusion of Exendin 9-39 in 1% human albumin in normal saline&#xD;
Exendin 9-39: Complete blockade of action of endogenous GLP-1 by Exendin 9-39.</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="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</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="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
              </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>Mr Geoffrey Roberts</name_or_title>
      <organization>University of Cambridge</organization>
      <phone>01223767176</phone>
      <email>geoffroberts@cantab.net</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/NCT02971631
org study id: A094265
secondary id: 218762
nct id: NCT02971631
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Patients who have undergone gastrectomy (removal of the stomach) to treat or prevent cancer
      are known to have a significantly reduced quality of life. To date, there is very little
      information on the physiological causes of this. The investigators suspect that
      overproduction of a hormone (chemical) called glucagon like peptide-1 (GLP-1) released by the
      lining of the gut may play a role in the reduced appetite, weight loss and low blood sugar
      symptoms seen in this group. To investigate this, the investigators will study the response
      of 16 patients who have previously had a gastrectomy to a glucose drink, and a meal, while
      receiving an infusion of a specific blocker of GLP-1 or placebo. The investigators will
      examine the levels of sugar and associated hormones in the blood, food consumption and food
      reward behaviour using standard tools.

      Participants will be invited to attend the Clinical Research Facility at Addenbrooke's
      Hospital for a screening visit, and two whole day study visits. The study has been designed
      to assess the role of overproduction of GLP-1 by completely blocking its actions, rather than
      assess the use of the blocking compound as a medication, and is therefore regarded as a
      physiological study, not a clinical trial.

      The goal of this study is to demonstrate the magnitude of effect of GLP-1 on blood sugar and
      appetite derangement in patients who have had a gastrectomy. This will guide future work on
      the development of novel treatment paradigms for the post-gastrectomy patient group.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Nadir Blood Glucose
time frame: As assessed during a 50g glucose tolerance test while receiving infusion of GLP-1 antagonist. At time 30-120 minutes of infusion of Exendin 9-39.
description: Lowest blood sugar reading during an oral glucose tolerance test while receiving infusion of GLP-1 antagonist. Please note participants will receive infusion of active compound for a maximum of four hours, with no expected effect of compound persisting for more than 30 minutes post-infusion.
measure: Total Insulin Secretion
time frame: Samples collected at 0, 15, 30, 45 and 60 minutes post oral glucose tolerance test.
description: 60 minute incremental area under the curve (i.e. total) insulin secretion during 50g oral glucose tolerance test while receiving infusion of GLP-1 antagonist. Please note participants will receive infusion of active compound for a maximum of four hours, with no expected effect of compound persisting for more than 30 minutes post-infusion.
measure: Eating Rate During ad Libitum Meal
time frame: 150-210 minutes during infusion of Exendin 9-39 or placebo.
description: As measured by universal eating monitor, total weight of a standardised meal consumed over a measured time in grams per minute.
measure: Decreased Hunger and Satiety Ratings During and After ad Libitum Meal
time frame: 150-240 minutes during infusion of Exendin 9-39 or placebo and for 4 hours post-cessation of infusion.
description: Will be measured on visual analogue scale and reported as a score out of 100. Higher value indicated more hunger and more satiety.
measure: Altered Food Attention.
time frame: 0-240 minutes during infusion of Exendin 9-39 or placebo, assessed on four occasions (baseline or T0, post-OGTT, pre-meal, post-meal) using a validated dot-probe visual response tool and reported in response time (milliseconds).
description: Food motivation can be measured by response rates to visual cues while being distracted by food related images. Will be measured with and without GLP-1 blockade to investigate effects of GLP-1 on food attention behaviour. Measure is of difference in response time when visual cue is colocated with a food related image vs a non-food related image, indicating degree of bias in attention to food images. Measure is undertaken during infusion at four timepoints - baseline (i.e. fasting), post oral glucose tolerance test (post-OGTT), before a standard meal (pre-meal) and after the meal (post-meal).
measure: Altered Food Motivation
time frame: 0-240 minutes during infusion of Exendin 9-39 or placebo (baseline or T0, post-OGTT, pre-m, assessed on four occasions using a validated grip strength surrogate of food motivation and measured as the area under the curve of a grip force monitoring curve.
description: Participant motivation to view particular food based cues is assessed by grip strength exerted to maintain those cues. Measure is undertaken during infusion at four timepoints - baseline (i.e. fasting), post oral glucose tolerance test (post-OGTT), before a standard meal (pre-meal) and after the meal (post-meal).
measure: Number of Participants With Infusion Related Adverse Events as Assessed by CTCAE v4
time frame: 24 hours from onset of infusion.
measure: Total Meal Consumption
time frame: 150-210 minutes during infusion of Exendin 9-39 or placebo
description: Total consumption amount of a standard meal during study intervention, measured in grams using a universal eating monitor.
arm group label: Placebo
arm group type: Placebo Comparator
description: Infusion of 1% human albumin in normal saline.
arm group label: Exendin
arm group type: Experimental
description: Infusion of Exendin 9-39 in 1% human albumin in normal saline
intervention type: Other
intervention name: Exendin 9-39
description: Complete blockade of action of endogenous GLP-1 by Exendin 9-39. Defined as a physiological study, not a clinical trial as such (as advised by the UK MHRA).
arm group label: Exendin
intervention type: Other
intervention name: Placebo
description: Infusion of 1% human albumin in normal saline
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: No
last name: Geoffrey Roberts, MA BM BCh
role: Principal Investigator
affiliation: University of Cambridge
facility: 
country: United Kingdom
responsible party type: Principal Investigator
investigator affiliation: Cambridge University Hospitals NHS Foundation Trust
investigator full name: Geoffrey Roberts
investigator title: Clinical Research Associate
mesh term: Dumping Syndrome
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 