<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/NCT03303196</url>
  </required_header>
  <id_info>
    <org_study_id>17-014144</org_study_id>
    <nct_id>NCT03303196</nct_id>
  </id_info>
  <brief_title>Bionic Pancreas in Children With Hyperinsulinism and Post-Pancreatectomy Diabetes</brief_title>
  <official_title>Bihormonal Bionic Pancreas for the Treatment of Diabetes Post-Pancreatectomy in Children With Congenital Hyperinsulinism - A Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Children's Hospital of Philadelphia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Boston University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Children's Hospital of Philadelphia</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_unapproved_device>Yes</is_unapproved_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a pilot study designed to determine if the bihormonal bionic pancreas provides&#xD;
      improved blood glucose control, compared to the current standard of care, in individuals with&#xD;
      hyperinsulinism who developed diabetes after having a pancreatectomy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The management of diabetes following pancreatectomy for hyperinsulinism (HI) generally&#xD;
      consists of the same approaches that are used for individuals with type 1 diabetes (T1D).&#xD;
      However, there are significant differences in individuals with HI and post-pancreatectomy&#xD;
      diabetes that increases the risk of hypoglycemia in these individuals and prevent achieving&#xD;
      tight glycemic control. Individuals with HI have glucagon deficiency and unlike T1D, those&#xD;
      with HI and post-pancreatectomy diabetes have residual dysregulated insulin secretion that&#xD;
      results in marked hypo- and hyper-glycemia. Furthermore, pancreatic insufficiency can result&#xD;
      in disturbances in nutrient absorption and fluctuations in glucose concentrations.&#xD;
&#xD;
      Current treatment approaches with intermittent subcutaneous insulin administration or insulin&#xD;
      pump therapy offer inadequate glycemic control in these individuals. We propose a novel&#xD;
      approach to the management of these individuals with the bihormonal bionic pancreas to&#xD;
      replace both hormones, insulin and glucagon, through an automated glycemic management system.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 9, 2018</start_date>
  <completion_date type="Actual">September 30, 2019</completion_date>
  <primary_completion_date type="Actual">September 30, 2019</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>
    <intervention_model_description>This will be an open-label, pilot clinical trial to assess efficacy and safety of the bihormonal bionic pancreas in children and young adults with HI who have developed post-pancreatectomy diabetes. Subjects will be studied during two research inpatient admissions at the CHOP HI Center. The order of the interventions will be randomized.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean Plasma Glucose Level.</measure>
    <time_frame>Days 2-3 of each admission</time_frame>
    <description>Mean plasma glucose concentration, as measured by the Continuous glucose monitoring system (CGMS), during the final 2 days of the Bihormonal Bionic Pancreas Admission compared to the Standard Care Admission.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Hyperinsulinism</condition>
  <condition>Diabetes</condition>
  <condition>Pancreatic Diseases</condition>
  <condition>Pancreatectomy; Hyperglycemia</condition>
  <arm_group>
    <arm_group_label>Bihormonal bionic pancreas admission</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Four day inpatient admission where participants will have blood sugar managed by the Bihormonal Bionic Pancreas. Blood sugars will be monitored for safety by study staff.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard care admission</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Four day inpatient admission where participants will have blood sugar managed by the participant's home-glucose control regimen. Blood sugars will be monitored for safety by study staff.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Bihormonal Bionic Pancreas</intervention_name>
    <description>A 4-day inpatient admission in which subjects will wear the bihormonal pancreas. The bihormonal pancreas will be placed upon admission and there will be 1 day of run-in. This will be followed by 3 days of data collection for comparison with the data obtained from the standard of care during the control admission.</description>
    <arm_group_label>Bihormonal bionic pancreas admission</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males or females age 6 to 30 years.&#xD;
&#xD;
          2. Diagnosis of hyperinsulinism.&#xD;
&#xD;
          3. Previous pancreatectomy.&#xD;
&#xD;
          4. Diabetes confirmed by one or more of the following:&#xD;
&#xD;
               -  Glycosylated A1c &gt; 6.4%.&#xD;
&#xD;
               -  Fasting glucose &gt; 125 mg/dL.&#xD;
&#xD;
               -  2-hour post-prandial glucose &gt; 200 mg/dL.&#xD;
&#xD;
               -  Random glucose &gt; 200 mg/dL with symptomatic hyperglycemia.&#xD;
&#xD;
          5. On insulin therapy with a regimen of at least 11 units/kg/day.&#xD;
&#xD;
          6. Treatment with subcutaneous insulin by pump at the time of recruitment.&#xD;
&#xD;
          7. Prescription medication regimen stable for &gt; 1 month (except for medications that will&#xD;
             not affect the safety of the study and are not expected to affect any outcome of the&#xD;
             study, in the judgment of the site PI).&#xD;
&#xD;
          8. Females &gt; 11 years of age must have a negative urine/serum pregnancy test and must use&#xD;
             an acceptable method of contraception, including abstinence, a barrier method&#xD;
             (diaphragm or condom), Depo-Provera, or an oral contraceptive, for the duration of the&#xD;
             study.&#xD;
&#xD;
          9. Informed consent, parental/guardian permission (informed consent) and if appropriate,&#xD;
             child assent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Unable to provide informed consent (e.g. impaired cognition or judgment).&#xD;
&#xD;
          2. Evidence of a medical condition that might alter results or compromise the&#xD;
             interpretation of results, including active infection, kidney failure, severe liver&#xD;
             dysfunction, severe respiratory or cardiac failure.&#xD;
&#xD;
          3. Evidence of severe hematologic abnormality including severe anemia and/or&#xD;
             thrombocytopenia.&#xD;
&#xD;
          4. Electrically powered implants (e.g. cochlear implants, neurostimulators) that might be&#xD;
             susceptible to radio frequency interference.&#xD;
&#xD;
          5. Unable to completely avoid acetaminophen for duration of study.&#xD;
&#xD;
          6. History of adverse reaction to glucagon (including allergy) besides nausea and&#xD;
             vomiting.&#xD;
&#xD;
          7. Established history of allergy or severe reaction to adhesive or tape that must be&#xD;
             used in the study.&#xD;
&#xD;
          8. Use oral (e.g. thiazolidinediones, biguanides, sulfonylureas, glitinides, dipeptidyl&#xD;
             peptidase-4 (DPP-4) inhibitors, Sodium-glucose Cotransporter-2 (SGLT-2) inhibitors&#xD;
             anti-diabetic medications.&#xD;
&#xD;
          9. Any investigational drug use within 30 days prior to enrollment.&#xD;
&#xD;
         10. Pregnant or lactating females.&#xD;
&#xD;
         11. Parents/guardians or subjects who, in the opinion of the Investigator, may be&#xD;
             non-compliant with study schedules or procedures.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>30 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Diva D De Leon, MD, MSCE</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Hospital of Philadelphia</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Arpana Rayannavar, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Hospital of Philadelphia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Hospital of Philadelphia</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.chop.edu/centers-programs/congenital-hyperinsulinism-center</url>
    <description>Children's Hospital of Philadelphia | Congenital Hyperinsulinism Center Website</description>
  </link>
  <link>
    <url>http://www.artificialpancreas.org/</url>
    <description>Boston University | Bionic Pancreas Website</description>
  </link>
  <reference>
    <citation>Russell SJ, El-Khatib FH, Nathan DM, Magyar KL, Jiang J, Damiano ER. Blood glucose control in type 1 diabetes with a bihormonal bionic endocrine pancreas. Diabetes Care. 2012 Nov;35(11):2148-55. doi: 10.2337/dc12-0071. Epub 2012 Aug 24.</citation>
    <PMID>22923666</PMID>
  </reference>
  <reference>
    <citation>El-Khatib FH, Russell SJ, Magyar KL, Sinha M, McKeon K, Nathan DM, Damiano ER. Autonomous and continuous adaptation of a bihormonal bionic pancreas in adults and adolescents with type 1 diabetes. J Clin Endocrinol Metab. 2014 May;99(5):1701-11. doi: 10.1210/jc.2013-4151. Epub 2014 Jan 31.</citation>
    <PMID>24483160</PMID>
  </reference>
  <reference>
    <citation>Russell SJ, Hillard MA, Balliro C, Magyar KL, Selagamsetty R, Sinha M, Grennan K, Mondesir D, Ekhlaspour L, Zheng H, Damiano ER, El-Khatib FH. Day and night glycaemic control with a bionic pancreas versus conventional insulin pump therapy in preadolescent children with type 1 diabetes: a randomised crossover trial. Lancet Diabetes Endocrinol. 2016 Mar;4(3):233-243. doi: 10.1016/S2213-8587(15)00489-1. Epub 2016 Feb 3. Erratum In: Lancet Diabetes Endocrinol. 2018 Mar;6(3):e3.</citation>
    <PMID>26850709</PMID>
  </reference>
  <reference>
    <citation>El-Khatib FH, Balliro C, Hillard MA, Magyar KL, Ekhlaspour L, Sinha M, Mondesir D, Esmaeili A, Hartigan C, Thompson MJ, Malkani S, Lock JP, Harlan DM, Clinton P, Frank E, Wilson DM, DeSalvo D, Norlander L, Ly T, Buckingham BA, Diner J, Dezube M, Young LA, Goley A, Kirkman MS, Buse JB, Zheng H, Selagamsetty RR, Damiano ER, Russell SJ. Home use of a bihormonal bionic pancreas versus insulin pump therapy in adults with type 1 diabetes: a multicentre randomised crossover trial. Lancet. 2017 Jan 28;389(10067):369-380. doi: 10.1016/S0140-6736(16)32567-3. Epub 2016 Dec 20. Erratum In: Lancet. 2017 Jan 28;389(10067):368. Lancet. 2017 Feb 4;389(10068):e2.</citation>
    <PMID>28007348</PMID>
  </reference>
  <reference>
    <citation>De Leon DD, Stanley CA. Mechanisms of Disease: advances in diagnosis and treatment of hyperinsulinism in neonates. Nat Clin Pract Endocrinol Metab. 2007 Jan;3(1):57-68. doi: 10.1038/ncpendmet0368.</citation>
    <PMID>17179930</PMID>
  </reference>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>October 2, 2017</study_first_submitted>
  <study_first_submitted_qc>October 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 5, 2017</study_first_posted>
  <results_first_submitted>August 18, 2020</results_first_submitted>
  <results_first_submitted_qc>October 2, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">October 27, 2020</results_first_posted>
  <last_update_submitted>October 2, 2020</last_update_submitted>
  <last_update_submitted_qc>October 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 27, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Children's Hospital of Philadelphia</investigator_affiliation>
    <investigator_full_name>Diva De Leon, MD, MSCE</investigator_full_name>
    <investigator_title>Director, Congenital Hyperinsulinism Center</investigator_title>
  </responsible_party>
  <keyword>Post-Pancreatectomy Diabetes</keyword>
  <keyword>Insulin Therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pancreatic Diseases</mesh_term>
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Hyperglycemia</mesh_term>
    <mesh_term>Hyperinsulinism</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pancrelipase</mesh_term>
  </intervention_browse>
  <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>December 22, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/96/NCT03303196/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Bihormonal Bionic Pancreas Admission</title>
          <description>Four day inpatient admission where participants will have blood sugar managed by the Bihormonal Bionic Pancreas. Blood sugars will be monitored for safety by study staff.</description>
        </group>
        <group group_id="P2">
          <title>Standard Care Admission</title>
          <description>Four day inpatient admission where participants will have blood sugar managed by the participant's home-glucose control regimen. Blood sugars will be monitored for safety by study staff.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5">Individuals who were assigned to BHBP admission then SC admission.</participants>
                <participants group_id="P2" count="5">Individuals who were assigned to SC admission then BHBP admission.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>Washout</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
              </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>Sequential Admissions</title>
          <description>Bihormonal bionic pancreas admission: Four day inpatient admission where participants will have blood sugar managed by the Bihormonal Bionic Pancreas. Blood sugars will be monitored for safety by study staff.&#xD;
*before or after* Standard care admission: Four day inpatient admission where participants will have blood sugar managed by the participant's home-glucose control regimen. Blood sugars will be monitored for safety by study staff.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="10"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15.1" lower_limit="7" upper_limit="25"/>
                  </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="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </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_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" 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>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Mean Plasma Glucose Level</title>
          <units>mmmol/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <title>Bionic Pancreas Admission</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8.3" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Standard Care Admission</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9.0" spread="1.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Mean Plasma Glucose Level.</title>
        <description>Mean plasma glucose concentration, as measured by the Continuous glucose monitoring system (CGMS), during the final 2 days of the Bihormonal Bionic Pancreas Admission compared to the Standard Care Admission.</description>
        <time_frame>Days 2-3 of each admission</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Sequential Admissions</title>
            <description>Bihormonal bionic pancreas admission: Four day inpatient admission where participants will have blood sugar managed by the Bihormonal Bionic Pancreas. Blood sugars will be monitored for safety by study staff.&#xD;
*before or after* Standard care admission: Four day inpatient admission where participants will have blood sugar managed by the participant's home-glucose control regimen. Blood sugars will be monitored for safety by study staff.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Plasma Glucose Level.</title>
          <description>Mean plasma glucose concentration, as measured by the Continuous glucose monitoring system (CGMS), during the final 2 days of the Bihormonal Bionic Pancreas Admission compared to the Standard Care Admission.</description>
          <units>mg/dL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Bihormonal Bionic Pancreas Admission</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="149.666118" spread="12.7998623"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Standard Care Admision</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="162.574753" spread="32.2642656"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data was collected from the start of screening until the end of the last day of the subject's second admission. This time period ranged from 16 to 38 days, depending on how many days in between admissions they had.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Bihormonal Bionic Pancreas Admission</title>
          <description>Four day inpatient admission where participants will have blood sugar managed by the Bihormonal Bionic Pancreas. Blood sugars will be monitored for safety by study staff.</description>
        </group>
        <group group_id="E2">
          <title>Standard Care Admission</title>
          <description>Four day inpatient admission where participants will have blood sugar managed by the participant's home-glucose control regimen. Blood sugars will be monitored for safety by study staff.</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>0</frequency_threshold>
        <default_vocab>NIH Safety Profiler</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Intermittent nasuea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="5"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" events="3" subjects_affected="3" 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>Lauren Mitteer</name_or_title>
      <organization>Children's Hospital of Philadelphia</organization>
      <phone>267-426-9915</phone>
      <email>MitteerL@email.chop.edu</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/NCT03303196
org study id: 17-014144
nct id: NCT03303196
lead sponsor: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: Yes
is unapproved device: Yes
This is a pilot study designed to determine if the bihormonal bionic pancreas provides
      improved blood glucose control, compared to the current standard of care, in individuals with
      hyperinsulinism who developed diabetes after having a pancreatectomy.
The management of diabetes following pancreatectomy for hyperinsulinism (HI) generally
      consists of the same approaches that are used for individuals with type 1 diabetes (T1D).
      However, there are significant differences in individuals with HI and post-pancreatectomy
      diabetes that increases the risk of hypoglycemia in these individuals and prevent achieving
      tight glycemic control. Individuals with HI have glucagon deficiency and unlike T1D, those
      with HI and post-pancreatectomy diabetes have residual dysregulated insulin secretion that
      results in marked hypo- and hyper-glycemia. Furthermore, pancreatic insufficiency can result
      in disturbances in nutrient absorption and fluctuations in glucose concentrations.

      Current treatment approaches with intermittent subcutaneous insulin administration or insulin
      pump therapy offer inadequate glycemic control in these individuals. We propose a novel
      approach to the management of these individuals with the bihormonal bionic pancreas to
      replace both hormones, insulin and glucagon, through an automated glycemic management system.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: This will be an open-label, pilot clinical trial to assess efficacy and safety of the bihormonal bionic pancreas in children and young adults with HI who have developed post-pancreatectomy diabetes. Subjects will be studied during two research inpatient admissions at the CHOP HI Center. The order of the interventions will be randomized.
primary purpose: Treatment
masking: None (Open Label)
measure: Mean Plasma Glucose Level.
time frame: Days 2-3 of each admission
description: Mean plasma glucose concentration, as measured by the Continuous glucose monitoring system (CGMS), during the final 2 days of the Bihormonal Bionic Pancreas Admission compared to the Standard Care Admission.
arm group label: Bihormonal bionic pancreas admission
arm group type: Experimental
description: Four day inpatient admission where participants will have blood sugar managed by the Bihormonal Bionic Pancreas. Blood sugars will be monitored for safety by study staff.
arm group label: Standard care admission
arm group type: No Intervention
description: Four day inpatient admission where participants will have blood sugar managed by the participant's home-glucose control regimen. Blood sugars will be monitored for safety by study staff.
intervention type: Device
intervention name: Bihormonal Bionic Pancreas
description: A 4-day inpatient admission in which subjects will wear the bihormonal pancreas. The bihormonal pancreas will be placed upon admission and there will be 1 day of run-in. This will be followed by 3 days of data collection for comparison with the data obtained from the standard of care during the control admission.
arm group label: Bihormonal bionic pancreas admission
criteria: 
gender: All
minimum age: 6 Years
maximum age: 30 Years
healthy volunteers: No
last name: Diva D De Leon, MD, MSCE
role: Principal Investigator
affiliation: Children's Hospital of Philadelphia
last name: Arpana Rayannavar, MD
role: Principal Investigator
affiliation: Children's Hospital of Philadelphia
facility: 
country: United States
url: http://www.chop.edu/centers-programs/congenital-hyperinsulinism-center
description: Children's Hospital of Philadelphia | Congenital Hyperinsulinism Center Website
url: http://www.artificialpancreas.org/
description: Boston University | Bionic Pancreas Website
citation: Russell SJ, El-Khatib FH, Nathan DM, Magyar KL, Jiang J, Damiano ER. Blood glucose control in type 1 diabetes with a bihormonal bionic endocrine pancreas. Diabetes Care. 2012 Nov;35(11):2148-55. doi: 10.2337/dc12-0071. Epub 2012 Aug 24.
PMID: 22923666
citation: El-Khatib FH, Russell SJ, Magyar KL, Sinha M, McKeon K, Nathan DM, Damiano ER. Autonomous and continuous adaptation of a bihormonal bionic pancreas in adults and adolescents with type 1 diabetes. J Clin Endocrinol Metab. 2014 May;99(5):1701-11. doi: 10.1210/jc.2013-4151. Epub 2014 Jan 31.
PMID: 24483160
citation: Russell SJ, Hillard MA, Balliro C, Magyar KL, Selagamsetty R, Sinha M, Grennan K, Mondesir D, Ekhlaspour L, Zheng H, Damiano ER, El-Khatib FH. Day and night glycaemic control with a bionic pancreas versus conventional insulin pump therapy in preadolescent children with type 1 diabetes: a randomised crossover trial. Lancet Diabetes Endocrinol. 2016 Mar;4(3):233-243. doi: 10.1016/S2213-8587(15)00489-1. Epub 2016 Feb 3. Erratum In: Lancet Diabetes Endocrinol. 2018 Mar;6(3):e3.
PMID: 26850709
citation: El-Khatib FH, Balliro C, Hillard MA, Magyar KL, Ekhlaspour L, Sinha M, Mondesir D, Esmaeili A, Hartigan C, Thompson MJ, Malkani S, Lock JP, Harlan DM, Clinton P, Frank E, Wilson DM, DeSalvo D, Norlander L, Ly T, Buckingham BA, Diner J, Dezube M, Young LA, Goley A, Kirkman MS, Buse JB, Zheng H, Selagamsetty RR, Damiano ER, Russell SJ. Home use of a bihormonal bionic pancreas versus insulin pump therapy in adults with type 1 diabetes: a multicentre randomised crossover trial. Lancet. 2017 Jan 28;389(10067):369-380. doi: 10.1016/S0140-6736(16)32567-3. Epub 2016 Dec 20. Erratum In: Lancet. 2017 Jan 28;389(10067):368. Lancet. 2017 Feb 4;389(10068):e2.
PMID: 28007348
citation: De Leon DD, Stanley CA. Mechanisms of Disease: advances in diagnosis and treatment of hyperinsulinism in neonates. Nat Clin Pract Endocrinol Metab. 2007 Jan;3(1):57-68. doi: 10.1038/ncpendmet0368.
PMID: 17179930
responsible party type: Principal Investigator
investigator affiliation: Children's Hospital of Philadelphia
investigator full name: Diva De Leon, MD, MSCE
investigator title: Director, Congenital Hyperinsulinism Center
mesh term: Pancreatic Diseases
mesh term: Diabetes Mellitus
mesh term: Hyperglycemia
mesh term: Hyperinsulinism
mesh term: Pancrelipase
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 