<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/NCT02204813</url>
  </required_header>
  <id_info>
    <org_study_id>08-0861F</org_study_id>
    <secondary_id>R01DK088126</secondary_id>
    <nct_id>NCT02204813</nct_id>
  </id_info>
  <brief_title>To Define the Role of GLP-1 for Improving Glucose Homeostasis in Humans Following Gastric Bypass Surgery</brief_title>
  <official_title>To Define the Role of GLP-1 for Improving Glucose Homeostasis in Humans Following Gastric Bypass Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Washington University School of Medicine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      There is a marked and long-lasting improvement in glucose homeostasis that follows Roux-en-y&#xD;
      gastric bypass surgery (RYGB) in humans. This improvement has been attributed in large part&#xD;
      to an intestinal hormone, called GLP-1, that is released into the circulation immediately&#xD;
      after eating. The purpose of this study is to determine if GLP-1 mediates the beneficial&#xD;
      effects of RYGB surgery on glucose homeostasis in humans.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      To conduct this study, we will enroll humans who previously underwent Roux-en-Y gastric&#xD;
      bypass surgery, who are medically and weight stable and with no signs of type 2 diabetes&#xD;
      either before or after surgery. Potential subjects will first be screened for eligibility and&#xD;
      also to verify that they can safely participate in the study. Each study subject will be&#xD;
      administered a meal tolerance test (MTT) on 3 separate occasions. For the MTT, a liquid meal&#xD;
      (Boost Plus) will be ingested following an overnight fast. A primed-continuous infusion of&#xD;
      vehicle alone (human albumin) or xenin-25 alone (at a dose of 4 or 12 pmoles x kg-1 x min-1)&#xD;
      will be initiated 15 minutes before the meal is ingested. Blood samples will be collected&#xD;
      before and during the MTT for the measurement of glucose and insulin levels, as well as a&#xD;
      host of other hormones. A comparison of the results will tell us if the effects of xenin-25&#xD;
      on insulin release are mediated by GLP-1 in humans.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 2014</start_date>
  <completion_date type="Actual">November 17, 2015</completion_date>
  <primary_completion_date type="Actual">November 17, 2015</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>Patients with prior RYGB surgery receive all interventions, each on a separate day.</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Insulin secretion rates (ISRs) during each treatment</measure>
    <time_frame>5.5 hours</time_frame>
    <description>ISRs will be measured at various times before and after ingestion of a liquid mixed meal.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Plasma glucose levels during each treatment.</measure>
    <time_frame>5.5 hours</time_frame>
    <description>Plasma glucose levels will be measured at various times before and after ingestion of a liquid mixed meal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma glucagon levels during each treatment.</measure>
    <time_frame>5.5 hours</time_frame>
    <description>Plasma glucagon levels will be measured at various times before and after ingestion of a liquid mixed meal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma GLP-1 during each treatment.</measure>
    <time_frame>5.5 hours</time_frame>
    <description>Plasma GLP-1 levels will be measured at various times before and after ingestion of a liquid mixed meal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma C-peptide levels during each treatment.</measure>
    <time_frame>5.5 hours</time_frame>
    <description>Plasma C-peptide levels will be measured at various times before and after ingestion of a liquid mixed meal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The rate of gastric emptying during each treatment.</measure>
    <time_frame>5.5 hours</time_frame>
    <description>The rate of gastric emptying will be estimated after ingestion of a liquid mixed meal.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">13</enrollment>
  <condition>Bypass, Gastric</condition>
  <condition>Roux-en-Y Gastric Bypass</condition>
  <condition>Vertical Sleeve Gastrectomy</condition>
  <condition>Gastric Banding</condition>
  <condition>Bariatric Surgery</condition>
  <arm_group>
    <arm_group_label>Post RYGB Surgery</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy, weight stable individuals, with previous Roux-en-Y gastric bypass surgery. No clinical evidence of type 2 diabetes before and after surgery. Each participant will receive placebo or the indicated doses of xenin-25.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>A liquid mixed meal containing 1.5 grams of acetaminophen will be ingested in 7 equal portions from 0-30 minutes.&#xD;
Starting at minus 15 minutes, an intravenous infusion of albumin alone (placebo) will be administered for 5.25 hours.</description>
    <arm_group_label>Post RYGB Surgery</arm_group_label>
    <other_name>Control</other_name>
    <other_name>Albumin Alone</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lo-Xenin</intervention_name>
    <description>A liquid mixed meal containing 1.5 grams of acetaminophen will be ingested in 7 equal portions from 0-30 minutes.&#xD;
Starting at minus 15 minutes, an intravenous infusion of xenin-25 at a dose of 4 pmoles/kg/min will be administered for 5.25 hours.</description>
    <arm_group_label>Post RYGB Surgery</arm_group_label>
    <other_name>Lo-Xen</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hi-Xenin</intervention_name>
    <description>A liquid mixed meal containing 1.5 grams of acetaminophen will be ingested in 7 equal portions from 0-30 minutes.&#xD;
Starting at minus 15 minutes, an intravenous infusion of xenin-25 at a dose of 12 pmoles/kg/min will be administered for 5.25 hours.</description>
    <arm_group_label>Post RYGB Surgery</arm_group_label>
    <other_name>Hi-Xen</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Extra Hi-Xenin</intervention_name>
    <description>A liquid mixed meal containing 1.5 grams of acetaminophen will be ingested in 7 equal portions from 0-30 minutes.&#xD;
Starting at minus 15 minutes, an intravenous infusion of xenin-25 at a dose of 24 pmoles/kg/min will be administered for 5.25 hours.</description>
    <arm_group_label>Post RYGB Surgery</arm_group_label>
    <other_name>XHi-Xen</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Individuals must be able to consent for their own participation (no mental impairment&#xD;
             affecting cognition or willingness to follow study instructions).&#xD;
&#xD;
          -  Healthy, weight stable, with previous Roux-en-Y gastric bypass surgery and no clinical&#xD;
             evidence of type 2 diabetes either before and after Roux-en-Y gastric bypass surgery.&#xD;
&#xD;
          -  Women of childbearing potential must be currently taking/using a method of birth&#xD;
             control that is acceptable to the investigators. A pregnancy test will be done at the&#xD;
             beginning of each visit. Any woman with a positive pregnancy test will be removed from&#xD;
             the study.&#xD;
&#xD;
          -  Willingness to return have 8-10ml of blood drawn 25-30 days after the last Xenin&#xD;
             infusion; to check for Xenin peptide antibodies that MAY develop. (All efforts will be&#xD;
             made to complete this visit during study participation.)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Lacks cognitive ability to sign the consent &amp;/or follow the study directions for&#xD;
             themselves.&#xD;
&#xD;
          -  Women unwilling to comply with using an acceptable method of contraception during the&#xD;
             course of the study, or who are currently breast-feeding.&#xD;
&#xD;
          -  Volunteers with a history of Acute Pancreatitis.&#xD;
&#xD;
          -  Volunteers with a history of cancer (except for skin cancer).&#xD;
&#xD;
          -  Volunteer with a history of Chronic Pancreatitis and/or risk factors for chronic&#xD;
             pancreatitis including hypertriglyceridemia (triglycerides &gt;400mg/ml) hypercalcemia&#xD;
             (blood calcium level &gt;11.md/dl) and/or the presence of gallstones.&#xD;
&#xD;
          -  Subjects taking medications known to affect glucose tolerance.&#xD;
&#xD;
          -  Hematocrit from the lab is below 33% (or if the finger stick hemoglobin measured with&#xD;
             the HemoCue 201+ is &lt;11.2 g/dl).&#xD;
&#xD;
          -  Any major medical conditions, or conditions that in the opinion of the PI make the&#xD;
             subject unsuitable for the study.&#xD;
&#xD;
          -  Subjects with abnormal kidney function as measured by the Creatinine concentration&#xD;
             will be excluded.&#xD;
&#xD;
          -  Subjects with a history of active liver disease or AST/ALT levels &gt;2X upper limit of&#xD;
             normal will also be excluded.&#xD;
&#xD;
          -  Total Bilirubin levels should be &lt;2.&#xD;
&#xD;
          -  Subjects unwilling to allow the use of their own blood or albumin in the preparation&#xD;
             of the peptides. (The blood will prevent sticking of the peptide to the tubing; an&#xD;
             alternative method has been sought but not found.)&#xD;
&#xD;
          -  Unwillingness to return have 8-10ml of blood drawn 25-30 days after the last Xenin&#xD;
             infusion; to check for Xenin peptide antibodies that MAY develop. (All efforts will be&#xD;
             made to complete this visit during study participation.)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Burton M Wice, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Washington University School of Medicine</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Dominic Reeds, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Washington University School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Sterl K, Wang S, Oestricker L, Wallendorf MJ, Patterson BW, Reeds DN, Wice BM. Metabolic responses to xenin-25 are altered in humans with Roux-en-Y gastric bypass surgery. Peptides. 2016 Aug;82:76-84. doi: 10.1016/j.peptides.2016.06.001. Epub 2016 Jun 7.</citation>
    <PMID>27288245</PMID>
  </results_reference>
  <verification_date>April 2018</verification_date>
  <study_first_submitted>July 28, 2014</study_first_submitted>
  <study_first_submitted_qc>July 28, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 30, 2014</study_first_posted>
  <last_update_submitted>April 25, 2018</last_update_submitted>
  <last_update_submitted_qc>April 25, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">April 27, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Gastric Bypass</keyword>
  <keyword>RYGB</keyword>
  <keyword>GLP-1</keyword>
  <keyword>Xenin</keyword>
  <keyword>Insulin Secretion</keyword>
  <keyword>Glucose Homeostasis</keyword>
  <keyword>Vertical Sleeve</keyword>
  <keyword>Lap Band</keyword>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT02204813
org study id: 08-0861F
secondary id: R01DK088126
nct id: NCT02204813
lead sponsor: 
collaborator: 
has dmc: Yes
There is a marked and long-lasting improvement in glucose homeostasis that follows Roux-en-y
      gastric bypass surgery (RYGB) in humans. This improvement has been attributed in large part
      to an intestinal hormone, called GLP-1, that is released into the circulation immediately
      after eating. The purpose of this study is to determine if GLP-1 mediates the beneficial
      effects of RYGB surgery on glucose homeostasis in humans.
To conduct this study, we will enroll humans who previously underwent Roux-en-Y gastric
      bypass surgery, who are medically and weight stable and with no signs of type 2 diabetes
      either before or after surgery. Potential subjects will first be screened for eligibility and
      also to verify that they can safely participate in the study. Each study subject will be
      administered a meal tolerance test (MTT) on 3 separate occasions. For the MTT, a liquid meal
      (Boost Plus) will be ingested following an overnight fast. A primed-continuous infusion of
      vehicle alone (human albumin) or xenin-25 alone (at a dose of 4 or 12 pmoles x kg-1 x min-1)
      will be initiated 15 minutes before the meal is ingested. Blood samples will be collected
      before and during the MTT for the measurement of glucose and insulin levels, as well as a
      host of other hormones. A comparison of the results will tell us if the effects of xenin-25
      on insulin release are mediated by GLP-1 in humans.
intervention model: Crossover Assignment
intervention model description: Patients with prior RYGB surgery receive all interventions, each on a separate day.
primary purpose: Basic Science
masking: Single (Participant)
measure: Insulin secretion rates (ISRs) during each treatment
time frame: 5.5 hours
description: ISRs will be measured at various times before and after ingestion of a liquid mixed meal.
measure: Plasma glucose levels during each treatment.
time frame: 5.5 hours
description: Plasma glucose levels will be measured at various times before and after ingestion of a liquid mixed meal.
measure: Plasma glucagon levels during each treatment.
time frame: 5.5 hours
description: Plasma glucagon levels will be measured at various times before and after ingestion of a liquid mixed meal.
measure: Plasma GLP-1 during each treatment.
time frame: 5.5 hours
description: Plasma GLP-1 levels will be measured at various times before and after ingestion of a liquid mixed meal.
measure: Plasma C-peptide levels during each treatment.
time frame: 5.5 hours
description: Plasma C-peptide levels will be measured at various times before and after ingestion of a liquid mixed meal.
measure: The rate of gastric emptying during each treatment.
time frame: 5.5 hours
description: The rate of gastric emptying will be estimated after ingestion of a liquid mixed meal.
arm group label: Post RYGB Surgery
arm group type: Experimental
description: Healthy, weight stable individuals, with previous Roux-en-Y gastric bypass surgery. No clinical evidence of type 2 diabetes before and after surgery. Each participant will receive placebo or the indicated doses of xenin-25.
intervention type: Drug
intervention name: Placebo
description: A liquid mixed meal containing 1.5 grams of acetaminophen will be ingested in 7 equal portions from 0-30 minutes.
Starting at minus 15 minutes, an intravenous infusion of albumin alone (placebo) will be administered for 5.25 hours.
arm group label: Post RYGB Surgery
other name: Control
other name: Albumin Alone
intervention type: Drug
intervention name: Lo-Xenin
description: A liquid mixed meal containing 1.5 grams of acetaminophen will be ingested in 7 equal portions from 0-30 minutes.
Starting at minus 15 minutes, an intravenous infusion of xenin-25 at a dose of 4 pmoles/kg/min will be administered for 5.25 hours.
arm group label: Post RYGB Surgery
other name: Lo-Xen
intervention type: Drug
intervention name: Hi-Xenin
description: A liquid mixed meal containing 1.5 grams of acetaminophen will be ingested in 7 equal portions from 0-30 minutes.
Starting at minus 15 minutes, an intravenous infusion of xenin-25 at a dose of 12 pmoles/kg/min will be administered for 5.25 hours.
arm group label: Post RYGB Surgery
other name: Hi-Xen
intervention type: Drug
intervention name: Extra Hi-Xenin
description: A liquid mixed meal containing 1.5 grams of acetaminophen will be ingested in 7 equal portions from 0-30 minutes.
Starting at minus 15 minutes, an intravenous infusion of xenin-25 at a dose of 24 pmoles/kg/min will be administered for 5.25 hours.
arm group label: Post RYGB Surgery
other name: XHi-Xen
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Burton M Wice, PhD
role: Principal Investigator
affiliation: Washington University School of Medicine
last name: Dominic Reeds, MD
role: Principal Investigator
affiliation: Washington University School of Medicine
facility: 
country: United States
citation: Sterl K, Wang S, Oestricker L, Wallendorf MJ, Patterson BW, Reeds DN, Wice BM. Metabolic responses to xenin-25 are altered in humans with Roux-en-Y gastric bypass surgery. Peptides. 2016 Aug;82:76-84. doi: 10.1016/j.peptides.2016.06.001. Epub 2016 Jun 7.
PMID: 27288245
responsible party type: Sponsor
sharing ipd: No