<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/NCT02996812</url>
  </required_header>
  <id_info>
    <org_study_id>34054</org_study_id>
    <nct_id>NCT02996812</nct_id>
  </id_info>
  <brief_title>Evaluation of Single Ascending Doses of Subcutaneous Exendin 9-39 in Patients With Post-Bariatric Hypoglycemia</brief_title>
  <official_title>Subcutaneous Injection of Exendin (9-39) in Subjects With Hyperinsulinemic Hypoglycemia Post-Bariatric Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tracey McLaughlin</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Stanford University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is designed to evaluate the safety, efficacy, and pharmacokinetic profile of&#xD;
      single ascending doses of exendin 9-39 administered by subcutaneous route in subjects with&#xD;
      post-bariatric hypoglycemia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Post-Bariatric Hypoglycemia (PBH) is a debilitating rare disease afflicting 0.2-6.9% of&#xD;
      post-bariatric patients, characterized by repeated severe hypoglycemic episodes with&#xD;
      neuroglycopenic symptoms and marked disability. There are no effective medical therapies.&#xD;
&#xD;
      While the cause is not known, exaggerated postprandial secretion of glucagon-like peptide-1&#xD;
      (GLP-1) as a result of altered nutrient transit likely plays a major role. GLP-1 is an&#xD;
      incretin hormone secreted primarily by the distal ileum that contributes to postprandial&#xD;
      glucose regulation. Exendin 9-39 (Ex9) is a specific GLP-1 receptor antagonist, that when&#xD;
      given via continuous IV infusion, has been shown to effectively prevent postprandial&#xD;
      hypoglycemia in patients with PBH. Subcutaneous (SC) injection of Ex9 may represent a safe,&#xD;
      effective and practical therapeutic approach to treating PBH.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>April 2015</start_date>
  <completion_date type="Anticipated">May 2017</completion_date>
  <primary_completion_date type="Actual">May 2016</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Treatment effect on plasma glucose</measure>
    <time_frame>0-180 minutes following initiation of oral glucose tolerance test (OGTT) conducted after treatment.</time_frame>
    <description>Magnitude of plasma glucose nadir during repeat OGTT after treatment</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Treatment effect on symptoms of hypoglycemia</measure>
    <time_frame>0-180 minutes following initiation of OGTT</time_frame>
    <description>Response rate in symptom score during repeat OGTT after treatment.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Hyperinsulinemia Hypoglycemia</condition>
  <arm_group>
    <arm_group_label>Dose A</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subcutaneous injection of Dose A of Exendin (9-39)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose B</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subcutaneous injection of Dose B of Exendin (9-39)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose C</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subcutaneous injection of Dose C of Exendin (9-39)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose D</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subcutaneous injection of Dose D of Exendin (9-39)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Exendin (9-39)</intervention_name>
    <arm_group_label>Dose A</arm_group_label>
    <arm_group_label>Dose B</arm_group_label>
    <arm_group_label>Dose C</arm_group_label>
    <arm_group_label>Dose D</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Post-bariatric surgery more than 6 months prior to signing the informed consent&#xD;
&#xD;
          -  Reported history of Whipple's triad: the occurrence of hypoglycemic symptoms&#xD;
             associated with blood glucose of ≤55 mg/dL, and resolution with glucose or&#xD;
             carbohydrate administration.&#xD;
&#xD;
          -  Symptomatic hypoglycemia during the baseline/screening OGTT, as defined by the&#xD;
             presence of plasma glucose ≤55 mg/dL with concomitant autonomic and/or neuroglycopenic&#xD;
             symptoms.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients currently using sulfonylureas or other medications that may interfere with&#xD;
             glucose metabolism within 5 half-lives of drug.&#xD;
&#xD;
          -  Participation in any clinical investigation within 4 weeks prior to dosing&#xD;
&#xD;
          -  History of or current insulinoma&#xD;
&#xD;
          -  Active infection or significant acute illness within 2 weeks prior to dosing&#xD;
&#xD;
          -  Female patients who are pregnant or lactating&#xD;
&#xD;
          -  Women of childbearing potential and not utilizing effective contraceptive methods&#xD;
&#xD;
          -  Inadequate end organ function&#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>Tracey McLaughlin, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Stanford University School of Medicine</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2016</verification_date>
  <study_first_submitted>December 15, 2016</study_first_submitted>
  <study_first_submitted_qc>December 15, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 19, 2016</study_first_posted>
  <last_update_submitted>December 15, 2016</last_update_submitted>
  <last_update_submitted_qc>December 15, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 19, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Stanford University</investigator_affiliation>
    <investigator_full_name>Tracey McLaughlin</investigator_full_name>
    <investigator_title>Associate Professor of Medicine (Endocrinology)</investigator_title>
  </responsible_party>
  <keyword>Post-bariatric hypoglycemia</keyword>
  <keyword>Non-insulinoma pancreatogenous hypoglycemia syndrome</keyword>
  <keyword>Late dumping syndrome</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypoglycemia</mesh_term>
    <mesh_term>Hyperinsulinism</mesh_term>
  </condition_browse>
  <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/NCT02996812
org study id: 34054
nct id: NCT02996812
lead sponsor: 
has dmc: Yes
This study is designed to evaluate the safety, efficacy, and pharmacokinetic profile of
      single ascending doses of exendin 9-39 administered by subcutaneous route in subjects with
      post-bariatric hypoglycemia.
Post-Bariatric Hypoglycemia (PBH) is a debilitating rare disease afflicting 0.2-6.9% of
      post-bariatric patients, characterized by repeated severe hypoglycemic episodes with
      neuroglycopenic symptoms and marked disability. There are no effective medical therapies.

      While the cause is not known, exaggerated postprandial secretion of glucagon-like peptide-1
      (GLP-1) as a result of altered nutrient transit likely plays a major role. GLP-1 is an
      incretin hormone secreted primarily by the distal ileum that contributes to postprandial
      glucose regulation. Exendin 9-39 (Ex9) is a specific GLP-1 receptor antagonist, that when
      given via continuous IV infusion, has been shown to effectively prevent postprandial
      hypoglycemia in patients with PBH. Subcutaneous (SC) injection of Ex9 may represent a safe,
      effective and practical therapeutic approach to treating PBH.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: Double (Participant, Care Provider)
measure: Treatment effect on plasma glucose
time frame: 0-180 minutes following initiation of oral glucose tolerance test (OGTT) conducted after treatment.
description: Magnitude of plasma glucose nadir during repeat OGTT after treatment
measure: Treatment effect on symptoms of hypoglycemia
time frame: 0-180 minutes following initiation of OGTT
description: Response rate in symptom score during repeat OGTT after treatment.
arm group label: Dose A
arm group type: Active Comparator
description: Subcutaneous injection of Dose A of Exendin (9-39)
arm group label: Dose B
arm group type: Active Comparator
description: Subcutaneous injection of Dose B of Exendin (9-39)
arm group label: Dose C
arm group type: Active Comparator
description: Subcutaneous injection of Dose C of Exendin (9-39)
arm group label: Dose D
arm group type: Active Comparator
description: Subcutaneous injection of Dose D of Exendin (9-39)
intervention type: Drug
intervention name: Exendin (9-39)
arm group label: Dose A
arm group label: Dose B
arm group label: Dose C
arm group label: Dose D
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Tracey McLaughlin, MD
role: Principal Investigator
affiliation: Stanford University
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Stanford University
investigator full name: Tracey McLaughlin
investigator title: Associate Professor of Medicine (Endocrinology)
mesh term: Hypoglycemia
mesh term: Hyperinsulinism
sharing ipd: No