<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/NCT02241889</url>
  </required_header>
  <id_info>
    <org_study_id>DP3-2014</org_study_id>
    <nct_id>NCT02241889</nct_id>
  </id_info>
  <brief_title>Three-way, Cross-over Closed-loop Exercise Study</brief_title>
  <official_title>A Randomized, Three-way, Cross-over Study to Assess the Efficacy of a Bi-hormonal Closed-loop System With vs Without Exercise Announcement vs Open-loop Therapy in Reducing Exercise-related Hypoglycemia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Oregon Health and Science University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Oregon Health and Science University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Blood glucose control systems that utilize both insulin and glucagon to manage blood sugar&#xD;
      are paving the way to revolutionize the management of this disease. The benefit of improved&#xD;
      control of blood sugar levels compared to standard insulin pump therapy has already been&#xD;
      demonstrated. However, the risk of low blood sugar in type 1 diabetes increases considerably&#xD;
      during exercise. The investigators research group has shown that small doses of glucagon can&#xD;
      prevent low blood sugar when used in a blood sugar control system in patients with type 1&#xD;
      diabetes. However, as insulin sensitivity changes occur very rapidly during exercise, the&#xD;
      ability to recognize the onset of physical activity in order to appropriately adjust the&#xD;
      insulin and glucagon delivery is vital to helping prevent exercise-induced hypoglycemia.&#xD;
&#xD;
      The purpose of this study is to test how well a new modified blood sugar control system&#xD;
      controls blood sugar during exercise compared to: 1) the current system without modifications&#xD;
      and 2) standard insulin pump therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Subjects will exercise during three study visits. During one visit, blood sugar will be&#xD;
      controlled using standard insulin pump therapy. The investigators blood glucose control&#xD;
      system will manage blood sugar for subjects during the other visits, with exercise&#xD;
      announcement with insulin and glucagon delivery modifications during one visit. Treatment&#xD;
      order will be randomized. Heart rate and accelerometry data will also be collected during&#xD;
      each visit for the purposes of designing an exercise detection system for future studies.&#xD;
&#xD;
      Each subject will be asked to undergo an eligibility screening and to sign a consent form&#xD;
      before any study procedures take place. At the screening appointment, after the consent form&#xD;
      is signed, blood will be drawn for laboratory tests and a brief physical exam will be&#xD;
      performed. An EKG and VO2max test will be completed at screening. Subjects that are enrolled&#xD;
      in the study will come in for a sensor insertion visit up to 72 hours before each study&#xD;
      visit. Subjects will undergo three 21-hour studies at an OHSU clinic or the OHSU clinical&#xD;
      research center. Subjects will arrive at the research center at 8pm. Approximately 2 hours&#xD;
      after a low-carbohydrate breakfast on Day 2, subjects will exercise for 45 minutes at 60% of&#xD;
      their VO2max determined at screening. Three hours after completion of exercise, subjects will&#xD;
      eat lunch. The study will end ~5 hours after lunch. Capillary blood glucose (CBG) will be&#xD;
      measured every 2 hours during the day, every 3 hours at night and before and after exercise&#xD;
      for studies using the blood glucose control system with subjects blinded to the CBG values.&#xD;
      For studies using insulin pump therapy, the subject will sample CBG four times during the day&#xD;
      as well as before and after exercise. Study staff will monitor studies remotely using a cloud&#xD;
      server. An investigator or nurse practitioner with a specialty in endocrinology or internal&#xD;
      medicine will be on site (located within the same complex) at all times.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2015</start_date>
  <completion_date type="Actual">September 2015</completion_date>
  <primary_completion_date type="Actual">September 2015</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>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percent of Time With Sensed Glucose &lt; 70 mg/dl</measure>
    <time_frame>from start of exercise (~hour 12) until study completion (hour 21)</time_frame>
    <description>Assess the percent of time that the Dexcom G4 or G4 Share reported sensor glucose values less than 70 mg/dl using Dexcom sensor downloads.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percent of Time With Sensed Glucose Between 70-180 mg/dl</measure>
    <time_frame>from start of exercise (~hour 12) until study completion (hour 21)</time_frame>
    <description>Assess the percent of time that the Dexcom G4 or G4 Share reported sensor glucose values between 70-180 mg/dl using Dexcom sensor downloads.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean of the Mean Sensed Glucose Per Participant</measure>
    <time_frame>Entire 21 hour study duration excluding the first four hours</time_frame>
    <description>Assess the mean sensed glucose per participant using Dexcom sensor downloads.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Carbohydrate Treatments</measure>
    <time_frame>Entire 21 hour study duration excluding the first four hours</time_frame>
    <description>Assess the number of rescue carbohydrate treatments.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent of Time With Sensed Glucose &lt; 50 mg/dl</measure>
    <time_frame>Entire 21 hour study duration excluding the first four hours</time_frame>
    <description>Assess the percent of time that the Dexcom G4 or G4 Share reported sensor glucose values less than 50 mg/dl using Dexcom sensor downloads.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent of Time With Sensed Glucose &gt; 180 mg/dl</measure>
    <time_frame>Entire 21 hour study duration excluding the first four hours</time_frame>
    <description>Assess the percent of time that the Dexcom G4 or G4 Share reported sensor glucose values greater than 180 mg/dl using Dexcom sensor downloads.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Events Capillary Blood Glucose (CBG) &lt;70 mg/dl</measure>
    <time_frame>Entire 21 hour study duration excluding the first four hours</time_frame>
    <description>Number of events measured with capillary blood glucose &lt;70 mg/dl.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Events With CBG Between 70 - 180 mg/dl</measure>
    <time_frame>Entire 21 hour study duration excluding the first four hours</time_frame>
    <description>Assess the number of events that the Contour Next BG meter reported blood glucose values between 70-180 mg/dl using meter downloads.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Events With CBG &lt;50 mg/dl</measure>
    <time_frame>Entire 21 hour study duration excluding the first four hours</time_frame>
    <description>Assess the total number of events that the Contour Next BG meter reported blood glucose values less than 50 mg/dl across all participants in each group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent of Time of CBG&gt;180 mg/dl</measure>
    <time_frame>Entire 21 hour study duration excluding the first four hours</time_frame>
    <description>Assess the percent of time that the Contour Next BG meter reported blood glucose values greater than 180 mg/dl using meter downloads.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">23</enrollment>
  <condition>Type 1 Diabetes</condition>
  <arm_group>
    <arm_group_label>Standard Insulin Pump Therapy</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects will undergo 21 hour study with exercise using Insulin pump therapy and managing their blood glucose as they normally would.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Closed-loop without adjustment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will undergo 21 study using the Closed-loop Artificial Pancreas Controller to manage blood sugar. Exercise will not be annouced to the controller and no adjustments to insulin and glucagon delivery will be made.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Closed-loop with adjustment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will undergo 21 hour study using the Closed-loop Artificial Pancreas Controller to manage blood sugar. Exercise will be annouced to the controller and adjustments to insulin and glucagon delivery will be made.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Insulin pump therapy</intervention_name>
    <description>Subject's own insulin pump will be used to manage blood glucose.</description>
    <arm_group_label>Standard Insulin Pump Therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Closed-loop Artificial Pancreas Controller</intervention_name>
    <description>Closed-loop Artificial Pancreas Controller includes insulin and glucagon delivery algorithm implemented on a smart phone, utilizing sensor glucose values from a Dexcom G4 sensor and sending delivery commands to two Tandem t:slim insulin pumps, one filled with insulin and one with glucagon.</description>
    <arm_group_label>Closed-loop with adjustment</arm_group_label>
    <arm_group_label>Closed-loop without adjustment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of type 1 diabetes mellitus for at least 1 year.&#xD;
&#xD;
          -  Male or female subjects 21 to 45 years of age.&#xD;
&#xD;
          -  Physically willing and able to perform 45 min of exercise (as determined by the&#xD;
             investigator after reviewing the subjects activity level)&#xD;
&#xD;
          -  Current use of an insulin pump.&#xD;
&#xD;
          -  Willingness to follow all study procedures, including attending all clinic visits.&#xD;
&#xD;
          -  Willingness to sign informed consent and HIPAA documents.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Female of childbearing potential who is pregnant or intending to become pregnant or&#xD;
             breast-feeding, or is not using adequate contraceptive methods. Acceptable&#xD;
             contraception includes birth control pill / patch / vaginal ring, Depo-Provera,&#xD;
             Norplant, an IUD, the double barrier method (the woman uses a diaphragm and spermicide&#xD;
             and the man uses a condom), or abstinence.&#xD;
&#xD;
          -  Any cardiovascular disease, defined as a clinically significant EKG abnormality at the&#xD;
             time of screening or any history of: stroke, heart failure, myocardial infarction,&#xD;
             angina pectoris, or coronary arterial bypass graft or angioplasty. Diagnosis of 2nd or&#xD;
             3rd degree heart block or any non-physiological arrhythmia judged by the investigator&#xD;
             to be exclusionary.&#xD;
&#xD;
          -  Renal insufficiency (GFR &lt; 60 ml/min, using the MDRD equation as report by the OHSU&#xD;
             laboratory).&#xD;
&#xD;
          -  Impaired liver function, defined as AST or ALT ≥2.5 times upper limit of normal,&#xD;
             according to OHSU laboratory reference ranges.&#xD;
&#xD;
          -  Hematocrit of less than or equal to 34%.&#xD;
&#xD;
          -  History of severe hypoglycemia during the past 12 months prior to screening visit or&#xD;
             hypoglycemia unawareness as judged by the investigator.&#xD;
&#xD;
          -  Adrenal insufficiency.&#xD;
&#xD;
          -  Any active infection.&#xD;
&#xD;
          -  Known or suspected abuse of alcohol, narcotics, or illicit drugs.&#xD;
&#xD;
          -  Seizure disorder.&#xD;
&#xD;
          -  Active foot ulceration.&#xD;
&#xD;
          -  Severe peripheral arterial disease characterized by ischemic rest pain or severe&#xD;
             claudication.&#xD;
&#xD;
          -  Major surgical operation within 30 days prior to screening.&#xD;
&#xD;
          -  Use of an investigational drug within 30 days prior to screening.&#xD;
&#xD;
          -  Chronic usage of any immunosuppressive medication (such as cyclosporine, azathioprine,&#xD;
             sirolimus, or tacrolimus).&#xD;
&#xD;
          -  Bleeding disorder, treatment with warfarin, or platelet count below 50,000.&#xD;
&#xD;
          -  Allergy to aspart insulin.&#xD;
&#xD;
          -  Allergy to glucagon.&#xD;
&#xD;
          -  Insulin resistance requiring more than 200 units per day.&#xD;
&#xD;
          -  Need for uninterrupted treatment of acetaminophen.&#xD;
&#xD;
          -  Current administration of oral or parenteral corticosteroids.&#xD;
&#xD;
          -  Any life threatening disease, including malignant neoplasms and medical history of&#xD;
             malignant neoplasms within the past 5 years prior to screening (except basal and&#xD;
             squamous cell skin cancer).&#xD;
&#xD;
          -  C peptide level of ≥0.5 ng/ml&#xD;
&#xD;
          -  Any concurrent illness, other than diabetes, that is not controlled by a stable&#xD;
             therapeutic regimen.&#xD;
&#xD;
          -  Beta blockers or non-dihydropyridine calcium channel blockers.&#xD;
&#xD;
          -  A positive response to any of the questions from the Physical Activity Readiness&#xD;
             Questionnaire.&#xD;
&#xD;
          -  Any clinically significant disease or disorder which in the opinion of the&#xD;
             Investigator may jeopardize the subject's safety or compliance with the protocol.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jessica Castle, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Oregon Health and Science University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Oregon Health and Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2017</verification_date>
  <study_first_submitted>September 12, 2014</study_first_submitted>
  <study_first_submitted_qc>September 15, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 16, 2014</study_first_posted>
  <results_first_submitted>September 7, 2016</results_first_submitted>
  <results_first_submitted_qc>April 13, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">May 22, 2017</results_first_posted>
  <last_update_submitted>April 13, 2017</last_update_submitted>
  <last_update_submitted_qc>April 13, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 22, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Oregon Health and Science University</investigator_affiliation>
    <investigator_full_name>Jessica Castle</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>diabetes</keyword>
  <keyword>closed-loop</keyword>
  <keyword>bi-hormonal</keyword>
  <keyword>exercise</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus, Type 1</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pancrelipase</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>SAP, APN, APX (21 Hours)</title>
          <description>The randomization order for subjects in this arm was open loop (Sensor Augmented Pump SAP), closed loop (APN) and closed loop with exercise announcement (APX). Each visit was 21 hours.</description>
        </group>
        <group group_id="P2">
          <title>SAP, APX, APN (21 Hours)</title>
          <description>The randomization order for subjects in this arm was open loop (Sensor Augmented Pump SAP), closed loop with exercise announcement (APX), and closed loop (APN). Each visit was 21 hours.</description>
        </group>
        <group group_id="P3">
          <title>APN, SAP and APX (21 Hours)</title>
          <description>The randomization order for subjects in this arm was closed loop (APN), open loop (Sensor Augmented Pump SAP), and closed loop with exercise announcement (APX). Each visit was 21 hours.</description>
        </group>
        <group group_id="P4">
          <title>APN, APX, SAP (21 Hours)</title>
          <description>The randomization order for subjects in this arm was closed loop (APN), closed loop with exercise announcement (APX), and open loop (Sensor Augmented Pump SAP). Each visit was 21 hours.</description>
        </group>
        <group group_id="P5">
          <title>APX, SAP, APN (21 Hours)</title>
          <description>The randomization order for subjects in this arm was closed loop with exercise announcement (APX), open loop (Sensor Augmented Pump SAP) and closed loop (APN). Each visit was 21 hours.</description>
        </group>
        <group group_id="P6">
          <title>APX, APN, SAP (21 Hours)</title>
          <description>The randomization order for subjects in this arm was closed loop with exercise announcement (APX), closed loop (APN) and open loop (Sensor Augmented Pump SAP). Each visit was 21 hours.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="3"/>
                <participants group_id="P5" count="5"/>
                <participants group_id="P6" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="3"/>
                <participants group_id="P5" count="5"/>
                <participants group_id="P6" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>device issues</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Type 1 diabetics using an insulin pump</population>
      <group_list>
        <group group_id="B1">
          <title>All Study Participants</title>
          <description>All study participants underwent three 21 hour study visits using either standard of care insulin pump therapy, closed loop control, or closed loop control with adjustments to insulin and glucagon after exercise announcement. Treatment order was randomized.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="23"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <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="23"/>
                  </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>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="32" spread="7"/>
                  </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="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </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="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percent of Time With Sensed Glucose &lt; 70 mg/dl</title>
        <description>Assess the percent of time that the Dexcom G4 or G4 Share reported sensor glucose values less than 70 mg/dl using Dexcom sensor downloads.</description>
        <time_frame>from start of exercise (~hour 12) until study completion (hour 21)</time_frame>
        <population>Data was analyzed from 21 subjects that completed all 3 visits and visits went to completion. No data was analyzed from the two subjects that did not complete all visits.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard Insulin Pump Therapy</title>
            <description>Subjects will undergo 21 hour study with exercise using Insulin pump therapy and managing their blood glucose as they normally would.&#xD;
Insulin pump therapy: Subject's own insulin pump will be used to manage blood glucose.</description>
          </group>
          <group group_id="O2">
            <title>Closed-loop Without Adjustment</title>
            <description>Subjects will undergo 21 hour study using the Closed-loop Artificial Pancreas Controller to manage blood sugar. Exercise will not be annouced to the controller and no adjustments to insulin and glucagon delivery will be made.&#xD;
Closed-loop Artificial Pancreas Controller: Closed-loop Artificial Pancreas Controller includes insulin and glucagon delivery algorithm implemented on a smart phone, utilizing sensor glucose values from a Dexcom G4 sensor and sending delivery commands to two Tandem t:slim insulin pumps, one filled with insulin and one with glucagon.</description>
          </group>
          <group group_id="O3">
            <title>Closed-loop With Adjustment</title>
            <description>Subjects will undergo 21 hour study using the Closed-loop Artificial Pancreas Controller to manage blood sugar. Exercise will be annouced to the controller and adjustments to insulin and glucagon delivery will be made.&#xD;
Closed-loop Artificial Pancreas Controller: Closed-loop Artificial Pancreas Controller includes insulin and glucagon delivery algorithm implemented on a smart phone, utilizing sensor glucose values from a Dexcom G4 sensor and sending delivery commands to two Tandem t:slim insulin pumps, one filled with insulin and one with glucagon.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent of Time With Sensed Glucose &lt; 70 mg/dl</title>
          <description>Assess the percent of time that the Dexcom G4 or G4 Share reported sensor glucose values less than 70 mg/dl using Dexcom sensor downloads.</description>
          <population>Data was analyzed from 21 subjects that completed all 3 visits and visits went to completion. No data was analyzed from the two subjects that did not complete all visits.</population>
          <units>percentage of time</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="21"/>
                <count group_id="O3" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.9" lower_limit="0.2" upper_limit="1.6"/>
                    <measurement group_id="O2" value="3.2" lower_limit="0.9" upper_limit="5.5"/>
                    <measurement group_id="O3" value="0.3" lower_limit="0.0" upper_limit="0.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percent of Time With Sensed Glucose Between 70-180 mg/dl</title>
        <description>Assess the percent of time that the Dexcom G4 or G4 Share reported sensor glucose values between 70-180 mg/dl using Dexcom sensor downloads.</description>
        <time_frame>from start of exercise (~hour 12) until study completion (hour 21)</time_frame>
        <population>Data was analyzed from 21 subjects that completed all 3 visits and visits went to completion. No data was analyzed from the two subjects that did not complete all visits.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard Insulin Pump Therapy</title>
            <description>Subjects will undergo 21 hour study with exercise using Insulin pump therapy and managing their blood glucose as they normally would.&#xD;
Insulin pump therapy: Subject's own insulin pump will be used to manage blood glucose.</description>
          </group>
          <group group_id="O2">
            <title>Closed-loop Without Adjustment</title>
            <description>Subjects will undergo 21 hour study using the Closed-loop Artificial Pancreas Controller to manage blood sugar. Exercise will not be annouced to the controller and no adjustments to insulin and glucagon delivery will be made.&#xD;
Closed-loop Artificial Pancreas Controller: Closed-loop Artificial Pancreas Controller includes insulin and glucagon delivery algorithm implemented on a smart phone, utilizing sensor glucose values from a Dexcom G4 sensor and sending delivery commands to two Tandem t:slim insulin pumps, one filled with insulin and one with glucagon.</description>
          </group>
          <group group_id="O3">
            <title>Closed-loop With Adjustment</title>
            <description>Subjects will undergo 21 hour study using the Closed-loop Artificial Pancreas Controller to manage blood sugar. Exercise will be annouced to the controller and adjustments to insulin and glucagon delivery will be made.&#xD;
Closed-loop Artificial Pancreas Controller: Closed-loop Artificial Pancreas Controller includes insulin and glucagon delivery algorithm implemented on a smart phone, utilizing sensor glucose values from a Dexcom G4 sensor and sending delivery commands to two Tandem t:slim insulin pumps, one filled with insulin and one with glucagon.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent of Time With Sensed Glucose Between 70-180 mg/dl</title>
          <description>Assess the percent of time that the Dexcom G4 or G4 Share reported sensor glucose values between 70-180 mg/dl using Dexcom sensor downloads.</description>
          <population>Data was analyzed from 21 subjects that completed all 3 visits and visits went to completion. No data was analyzed from the two subjects that did not complete all visits.</population>
          <units>percent of time</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="21"/>
                <count group_id="O3" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="67.6" lower_limit="59.5" upper_limit="75.7"/>
                    <measurement group_id="O2" value="72.5" lower_limit="66.3" upper_limit="78.8"/>
                    <measurement group_id="O3" value="67.3" lower_limit="60.2" upper_limit="74.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean of the Mean Sensed Glucose Per Participant</title>
        <description>Assess the mean sensed glucose per participant using Dexcom sensor downloads.</description>
        <time_frame>Entire 21 hour study duration excluding the first four hours</time_frame>
        <population>Data was analyzed from 21 subjects that completed all 3 visits and visits went to completion. No data was analyzed from the two subjects that did not complete all visits.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard Insulin Pump Therapy</title>
            <description>Subjects will undergo 21 hour study with exercise using Insulin pump therapy and managing their blood glucose as they normally would.&#xD;
Insulin pump therapy: Subject's own insulin pump will be used to manage blood glucose.</description>
          </group>
          <group group_id="O2">
            <title>Closed-loop Without Adjustment</title>
            <description>Subjects will undergo 21 hour study using the Closed-loop Artificial Pancreas Controller to manage blood sugar. Exercise will not be annouced to the controller and no adjustments to insulin and glucagon delivery will be made.&#xD;
Closed-loop Artificial Pancreas Controller: Closed-loop Artificial Pancreas Controller includes insulin and glucagon delivery algorithm implemented on a smart phone, utilizing sensor glucose values from a Dexcom G4 sensor and sending delivery commands to two Tandem t:slim insulin pumps, one filled with insulin and one with glucagon.</description>
          </group>
          <group group_id="O3">
            <title>Closed-loop With Adjustment</title>
            <description>Subjects will undergo 21 hour study using the Closed-loop Artificial Pancreas Controller to manage blood sugar. Exercise will be annouced to the controller and adjustments to insulin and glucagon delivery will be made.&#xD;
Closed-loop Artificial Pancreas Controller: Closed-loop Artificial Pancreas Controller includes insulin and glucagon delivery algorithm implemented on a smart phone, utilizing sensor glucose values from a Dexcom G4 sensor and sending delivery commands to two Tandem t:slim insulin pumps, one filled with insulin and one with glucagon.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean of the Mean Sensed Glucose Per Participant</title>
          <description>Assess the mean sensed glucose per participant using Dexcom sensor downloads.</description>
          <population>Data was analyzed from 21 subjects that completed all 3 visits and visits went to completion. No data was analyzed from the two subjects that did not complete all visits.</population>
          <units>mg/dl</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="21"/>
                <count group_id="O3" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.6" lower_limit="7.9" upper_limit="9.2"/>
                    <measurement group_id="O2" value="8.0" lower_limit="7.8" upper_limit="8.3"/>
                    <measurement group_id="O3" value="8.6" lower_limit="8.1" upper_limit="9.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Carbohydrate Treatments</title>
        <description>Assess the number of rescue carbohydrate treatments.</description>
        <time_frame>Entire 21 hour study duration excluding the first four hours</time_frame>
        <population>Data was analyzed from 21 subjects that completed all 3 visits and visits went to completion. No data was analyzed from the two subjects that did not complete all visits.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard Insulin Pump Therapy</title>
            <description>Subjects will undergo 21 hour study with exercise using Insulin pump therapy and managing their blood glucose as they normally would.&#xD;
Insulin pump therapy: Subject's own insulin pump will be used to manage blood glucose.</description>
          </group>
          <group group_id="O2">
            <title>Closed-loop Without Adjustment</title>
            <description>Subjects will undergo 21 hour study using the Closed-loop Artificial Pancreas Controller to manage blood sugar. Exercise will not be annouced to the controller and no adjustments to insulin and glucagon delivery will be made.&#xD;
Closed-loop Artificial Pancreas Controller: Closed-loop Artificial Pancreas Controller includes insulin and glucagon delivery algorithm implemented on a smart phone, utilizing sensor glucose values from a Dexcom G4 sensor and sending delivery commands to two Tandem t:slim insulin pumps, one filled with insulin and one with glucagon.</description>
          </group>
          <group group_id="O3">
            <title>Closed-loop With Adjustment</title>
            <description>Subjects will undergo 21 hour study using the Closed-loop Artificial Pancreas Controller to manage blood sugar. Exercise will be annouced to the controller and adjustments to insulin and glucagon delivery will be made.&#xD;
Closed-loop Artificial Pancreas Controller: Closed-loop Artificial Pancreas Controller includes insulin and glucagon delivery algorithm implemented on a smart phone, utilizing sensor glucose values from a Dexcom G4 sensor and sending delivery commands to two Tandem t:slim insulin pumps, one filled with insulin and one with glucagon.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Carbohydrate Treatments</title>
          <description>Assess the number of rescue carbohydrate treatments.</description>
          <population>Data was analyzed from 21 subjects that completed all 3 visits and visits went to completion. No data was analyzed from the two subjects that did not complete all visits.</population>
          <units>carbohydrate treatments</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="21"/>
                <count group_id="O3" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.33" lower_limit="0.09" upper_limit="0.58"/>
                    <measurement group_id="O2" value="0.43" lower_limit="0.15" upper_limit="0.71"/>
                    <measurement group_id="O3" value="0.29" lower_limit="0.06" upper_limit="0.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent of Time With Sensed Glucose &lt; 50 mg/dl</title>
        <description>Assess the percent of time that the Dexcom G4 or G4 Share reported sensor glucose values less than 50 mg/dl using Dexcom sensor downloads.</description>
        <time_frame>Entire 21 hour study duration excluding the first four hours</time_frame>
        <population>Data was analyzed from 21 subjects that completed all 3 visits and visits went to completion. No data was analyzed from the two subjects that did not complete all visits.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard Insulin Pump Therapy</title>
            <description>Subjects will undergo 21 hour study with exercise using Insulin pump therapy and managing their blood glucose as they normally would.&#xD;
Insulin pump therapy: Subject's own insulin pump will be used to manage blood glucose.</description>
          </group>
          <group group_id="O2">
            <title>Closed-loop Without Adjustment</title>
            <description>Subjects will undergo 21 hour study using the Closed-loop Artificial Pancreas Controller to manage blood sugar. Exercise will not be annouced to the controller and no adjustments to insulin and glucagon delivery will be made.&#xD;
Closed-loop Artificial Pancreas Controller: Closed-loop Artificial Pancreas Controller includes insulin and glucagon delivery algorithm implemented on a smart phone, utilizing sensor glucose values from a Dexcom G4 sensor and sending delivery commands to two Tandem t:slim insulin pumps, one filled with insulin and one with glucagon.</description>
          </group>
          <group group_id="O3">
            <title>Closed-loop With Adjustment</title>
            <description>Subjects will undergo 21 hour study using the Closed-loop Artificial Pancreas Controller to manage blood sugar. Exercise will be annouced to the controller and adjustments to insulin and glucagon delivery will be made.&#xD;
Closed-loop Artificial Pancreas Controller: Closed-loop Artificial Pancreas Controller includes insulin and glucagon delivery algorithm implemented on a smart phone, utilizing sensor glucose values from a Dexcom G4 sensor and sending delivery commands to two Tandem t:slim insulin pumps, one filled with insulin and one with glucagon.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent of Time With Sensed Glucose &lt; 50 mg/dl</title>
          <description>Assess the percent of time that the Dexcom G4 or G4 Share reported sensor glucose values less than 50 mg/dl using Dexcom sensor downloads.</description>
          <population>Data was analyzed from 21 subjects that completed all 3 visits and visits went to completion. No data was analyzed from the two subjects that did not complete all visits.</population>
          <units>percent of time</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="21"/>
                <count group_id="O3" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.001" lower_limit="0.000" upper_limit="0.03"/>
                    <measurement group_id="O2" value="0.001" lower_limit="0.000" upper_limit="0.002"/>
                    <measurement group_id="O3" value="0.0" lower_limit="0.000" upper_limit="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent of Time With Sensed Glucose &gt; 180 mg/dl</title>
        <description>Assess the percent of time that the Dexcom G4 or G4 Share reported sensor glucose values greater than 180 mg/dl using Dexcom sensor downloads.</description>
        <time_frame>Entire 21 hour study duration excluding the first four hours</time_frame>
        <population>Data was analyzed from 21 subjects that completed all 3 visits and visits went to completion. No data was analyzed from the two subjects that did not complete all visits.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard Insulin Pump Therapy</title>
            <description>Subjects will undergo 21 hour study with exercise using Insulin pump therapy and managing their blood glucose as they normally would.&#xD;
Insulin pump therapy: Subject's own insulin pump will be used to manage blood glucose.</description>
          </group>
          <group group_id="O2">
            <title>Closed-loop Without Adjustment</title>
            <description>Subjects will undergo 21 hour study using the Closed-loop Artificial Pancreas Controller to manage blood sugar. Exercise will not be annouced to the controller and no adjustments to insulin and glucagon delivery will be made.&#xD;
Closed-loop Artificial Pancreas Controller: Closed-loop Artificial Pancreas Controller includes insulin and glucagon delivery algorithm implemented on a smart phone, utilizing sensor glucose values from a Dexcom G4 sensor and sending delivery commands to two Tandem t:slim insulin pumps, one filled with insulin and one with glucagon.</description>
          </group>
          <group group_id="O3">
            <title>Closed-loop With Adjustment</title>
            <description>Subjects will undergo 21 hour study using the Closed-loop Artificial Pancreas Controller to manage blood sugar. Exercise will be annouced to the controller and adjustments to insulin and glucagon delivery will be made.&#xD;
Closed-loop Artificial Pancreas Controller: Closed-loop Artificial Pancreas Controller includes insulin and glucagon delivery algorithm implemented on a smart phone, utilizing sensor glucose values from a Dexcom G4 sensor and sending delivery commands to two Tandem t:slim insulin pumps, one filled with insulin and one with glucagon.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent of Time With Sensed Glucose &gt; 180 mg/dl</title>
          <description>Assess the percent of time that the Dexcom G4 or G4 Share reported sensor glucose values greater than 180 mg/dl using Dexcom sensor downloads.</description>
          <population>Data was analyzed from 21 subjects that completed all 3 visits and visits went to completion. No data was analyzed from the two subjects that did not complete all visits.</population>
          <units>percent of time</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="21"/>
                <count group_id="O3" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.9" lower_limit="19.8" upper_limit="34.1"/>
                    <measurement group_id="O2" value="16.9" lower_limit="13.2" upper_limit="20.6"/>
                    <measurement group_id="O3" value="25.2" lower_limit="18.7" upper_limit="31.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Events Capillary Blood Glucose (CBG) &lt;70 mg/dl</title>
        <description>Number of events measured with capillary blood glucose &lt;70 mg/dl.</description>
        <time_frame>Entire 21 hour study duration excluding the first four hours</time_frame>
        <population>Data was analyzed from 21 subjects that completed all 3 visits and visits went to completion. No data was analyzed from the two subjects that did not complete all visits.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard Insulin Pump Therapy</title>
            <description>Subjects will undergo 21 hour study with exercise using Insulin pump therapy and managing their blood glucose as they normally would.&#xD;
Insulin pump therapy: Subject's own insulin pump will be used to manage blood glucose.</description>
          </group>
          <group group_id="O2">
            <title>Closed-loop Without Adjustment</title>
            <description>Subjects will undergo 21 hour study using the Closed-loop Artificial Pancreas Controller to manage blood sugar. Exercise will not be annouced to the controller and no adjustments to insulin and glucagon delivery will be made.&#xD;
Closed-loop Artificial Pancreas Controller: Closed-loop Artificial Pancreas Controller includes insulin and glucagon delivery algorithm implemented on a smart phone, utilizing sensor glucose values from a Dexcom G4 sensor and sending delivery commands to two Tandem t:slim insulin pumps, one filled with insulin and one with glucagon.</description>
          </group>
          <group group_id="O3">
            <title>Closed-loop With Adjustment</title>
            <description>Subjects will undergo 21 hour study using the Closed-loop Artificial Pancreas Controller to manage blood sugar. Exercise will be annouced to the controller and adjustments to insulin and glucagon delivery will be made.&#xD;
Closed-loop Artificial Pancreas Controller: Closed-loop Artificial Pancreas Controller includes insulin and glucagon delivery algorithm implemented on a smart phone, utilizing sensor glucose values from a Dexcom G4 sensor and sending delivery commands to two Tandem t:slim insulin pumps, one filled with insulin and one with glucagon.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Events Capillary Blood Glucose (CBG) &lt;70 mg/dl</title>
          <description>Number of events measured with capillary blood glucose &lt;70 mg/dl.</description>
          <population>Data was analyzed from 21 subjects that completed all 3 visits and visits went to completion. No data was analyzed from the two subjects that did not complete all visits.</population>
          <units>occurrences of blood glucose &lt; 70 mg/dl</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="21"/>
                <count group_id="O3" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.43" lower_limit="0.15" upper_limit="0.71"/>
                    <measurement group_id="O2" value="0.33" lower_limit="0.09" upper_limit="0.58"/>
                    <measurement group_id="O3" value="0.24" lower_limit="0.03" upper_limit="0.45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Events With CBG Between 70 - 180 mg/dl</title>
        <description>Assess the number of events that the Contour Next BG meter reported blood glucose values between 70-180 mg/dl using meter downloads.</description>
        <time_frame>Entire 21 hour study duration excluding the first four hours</time_frame>
        <population>Data was analyzed from 21 subjects that completed all 3 visits and visits went to completion. No data was analyzed from the two subjects that did not complete all visits.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard Insulin Pump Therapy</title>
            <description>Subjects will undergo 21 hour study with exercise using Insulin pump therapy and managing their blood glucose as they normally would.&#xD;
Insulin pump therapy: Subject's own insulin pump will be used to manage blood glucose.</description>
          </group>
          <group group_id="O2">
            <title>Closed-loop Without Adjustment</title>
            <description>Subjects will undergo 21 hour study using the Closed-loop Artificial Pancreas Controller to manage blood sugar. Exercise will not be annouced to the controller and no adjustments to insulin and glucagon delivery will be made.&#xD;
Closed-loop Artificial Pancreas Controller: Closed-loop Artificial Pancreas Controller includes insulin and glucagon delivery algorithm implemented on a smart phone, utilizing sensor glucose values from a Dexcom G4 sensor and sending delivery commands to two Tandem t:slim insulin pumps, one filled with insulin and one with glucagon.</description>
          </group>
          <group group_id="O3">
            <title>Closed-loop With Adjustment</title>
            <description>Subjects will undergo 21 hour study using the Closed-loop Artificial Pancreas Controller to manage blood sugar. Exercise will be annouced to the controller and adjustments to insulin and glucagon delivery will be made.&#xD;
Closed-loop Artificial Pancreas Controller: Closed-loop Artificial Pancreas Controller includes insulin and glucagon delivery algorithm implemented on a smart phone, utilizing sensor glucose values from a Dexcom G4 sensor and sending delivery commands to two Tandem t:slim insulin pumps, one filled with insulin and one with glucagon.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Events With CBG Between 70 - 180 mg/dl</title>
          <description>Assess the number of events that the Contour Next BG meter reported blood glucose values between 70-180 mg/dl using meter downloads.</description>
          <population>Data was analyzed from 21 subjects that completed all 3 visits and visits went to completion. No data was analyzed from the two subjects that did not complete all visits.</population>
          <units># of events</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="21"/>
                <count group_id="O3" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.6" lower_limit="1.3" upper_limit="1.9"/>
                    <measurement group_id="O2" value="3.1" lower_limit="2.7" upper_limit="3.5"/>
                    <measurement group_id="O3" value="3.0" lower_limit="2.6" upper_limit="3.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Events With CBG &lt;50 mg/dl</title>
        <description>Assess the total number of events that the Contour Next BG meter reported blood glucose values less than 50 mg/dl across all participants in each group.</description>
        <time_frame>Entire 21 hour study duration excluding the first four hours</time_frame>
        <population>Data was analyzed from 21 subjects that completed all 3 visits and visits went to completion. No data was analyzed from the two subjects that did not complete all visits.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard Insulin Pump Therapy</title>
            <description>Subjects will undergo 21 hour study with exercise using Insulin pump therapy and managing their blood glucose as they normally would.&#xD;
Insulin pump therapy: Subject's own insulin pump will be used to manage blood glucose.</description>
          </group>
          <group group_id="O2">
            <title>Closed-loop Without Adjustment</title>
            <description>Subjects will undergo 21 hour study using the Closed-loop Artificial Pancreas Controller to manage blood sugar. Exercise will not be annouced to the controller and no adjustments to insulin and glucagon delivery will be made.&#xD;
Closed-loop Artificial Pancreas Controller: Closed-loop Artificial Pancreas Controller includes insulin and glucagon delivery algorithm implemented on a smart phone, utilizing sensor glucose values from a Dexcom G4 sensor and sending delivery commands to two Tandem t:slim insulin pumps, one filled with insulin and one with glucagon.</description>
          </group>
          <group group_id="O3">
            <title>Closed-loop With Adjustment</title>
            <description>Subjects will undergo 21 hour study using the Closed-loop Artificial Pancreas Controller to manage blood sugar. Exercise will be annouced to the controller and adjustments to insulin and glucagon delivery will be made.&#xD;
Closed-loop Artificial Pancreas Controller: Closed-loop Artificial Pancreas Controller includes insulin and glucagon delivery algorithm implemented on a smart phone, utilizing sensor glucose values from a Dexcom G4 sensor and sending delivery commands to two Tandem t:slim insulin pumps, one filled with insulin and one with glucagon.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Events With CBG &lt;50 mg/dl</title>
          <description>Assess the total number of events that the Contour Next BG meter reported blood glucose values less than 50 mg/dl across all participants in each group.</description>
          <population>Data was analyzed from 21 subjects that completed all 3 visits and visits went to completion. No data was analyzed from the two subjects that did not complete all visits.</population>
          <units>occurrences of blood glucose &lt; 50 mg/dl</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="21"/>
                <count group_id="O3" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent of Time of CBG&gt;180 mg/dl</title>
        <description>Assess the percent of time that the Contour Next BG meter reported blood glucose values greater than 180 mg/dl using meter downloads.</description>
        <time_frame>Entire 21 hour study duration excluding the first four hours</time_frame>
        <population>Data was analyzed from 21 subjects that completed all 3 visits and visits went to completion. No data was analyzed from the two subjects that did not complete all visits.</population>
        <group_list>
          <group group_id="O1">
            <title>Standard Insulin Pump Therapy</title>
            <description>Subjects will undergo 21 hour study with exercise using Insulin pump therapy and managing their blood glucose as they normally would.&#xD;
Insulin pump therapy: Subject's own insulin pump will be used to manage blood glucose.</description>
          </group>
          <group group_id="O2">
            <title>Closed-loop Without Adjustment</title>
            <description>Subjects will undergo 21 hour study using the Closed-loop Artificial Pancreas Controller to manage blood sugar. Exercise will not be annouced to the controller and no adjustments to insulin and glucagon delivery will be made.&#xD;
Closed-loop Artificial Pancreas Controller: Closed-loop Artificial Pancreas Controller includes insulin and glucagon delivery algorithm implemented on a smart phone, utilizing sensor glucose values from a Dexcom G4 sensor and sending delivery commands to two Tandem t:slim insulin pumps, one filled with insulin and one with glucagon.</description>
          </group>
          <group group_id="O3">
            <title>Closed-loop With Adjustment</title>
            <description>Subjects will undergo 21 hour study using the Closed-loop Artificial Pancreas Controller to manage blood sugar. Exercise will be annouced to the controller and adjustments to insulin and glucagon delivery will be made.&#xD;
Closed-loop Artificial Pancreas Controller: Closed-loop Artificial Pancreas Controller includes insulin and glucagon delivery algorithm implemented on a smart phone, utilizing sensor glucose values from a Dexcom G4 sensor and sending delivery commands to two Tandem t:slim insulin pumps, one filled with insulin and one with glucagon.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent of Time of CBG&gt;180 mg/dl</title>
          <description>Assess the percent of time that the Contour Next BG meter reported blood glucose values greater than 180 mg/dl using meter downloads.</description>
          <population>Data was analyzed from 21 subjects that completed all 3 visits and visits went to completion. No data was analyzed from the two subjects that did not complete all visits.</population>
          <units>percentage of time</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="21"/>
                <count group_id="O3" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.1" lower_limit="0.7" upper_limit="1.4"/>
                    <measurement group_id="O2" value="0.7" lower_limit="0.4" upper_limit="1.0"/>
                    <measurement group_id="O3" value="1.1" lower_limit="0.6" upper_limit="1.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>9 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Standard Insulin Pump Therapy</title>
          <description>Subjects will undergo 21 hour study with exercise using Insulin pump therapy and managing their blood glucose as they normally would.&#xD;
Insulin pump therapy: Subject's own insulin pump will be used to manage blood glucose.</description>
        </group>
        <group group_id="E2">
          <title>Closed-loop Without Adjustment</title>
          <description>Subjects will undergo 21 study using the Closed-loop Artificial Pancreas Controller to manage blood sugar. Exercise will not be annouced to the controller and no adjustments to insulin and glucagon delivery will be made.&#xD;
Closed-loop Artificial Pancreas Controller: Closed-loop Artificial Pancreas Controller includes insulin and glucagon delivery algorithm implemented on a smart phone, utilizing sensor glucose values from a Dexcom G4 sensor and sending delivery commands to two Tandem t:slim insulin pumps, one filled with insulin and one with glucagon.</description>
        </group>
        <group group_id="E3">
          <title>Closed-loop With Adjustment</title>
          <description>Subjects will undergo 21 hour study using the Closed-loop Artificial Pancreas Controller to manage blood sugar. Exercise will be annouced to the controller and adjustments to insulin and glucagon delivery will be made.&#xD;
Closed-loop Artificial Pancreas Controller: Closed-loop Artificial Pancreas Controller includes insulin and glucagon delivery algorithm implemented on a smart phone, utilizing sensor glucose values from a Dexcom G4 sensor and sending delivery commands to two Tandem t:slim insulin pumps, one filled with insulin and one with glucagon.</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="23"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-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="1" subjects_at_risk="23"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="23"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="23"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>chills</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </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="23"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>ligh headedness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>mild edema</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="23"/>
              </event>
              <event>
                <sub_title>rash</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="23"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="23"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="23"/>
              </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>Dr. Jessica Castle</name_or_title>
      <organization>Oregon Health and Science University</organization>
      <phone>503-494-7072</phone>
      <email>castleje@ohsu.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/NCT02241889
org study id: DP3-2014
nct id: NCT02241889
lead sponsor: 
has dmc: No
Blood glucose control systems that utilize both insulin and glucagon to manage blood sugar
      are paving the way to revolutionize the management of this disease. The benefit of improved
      control of blood sugar levels compared to standard insulin pump therapy has already been
      demonstrated. However, the risk of low blood sugar in type 1 diabetes increases considerably
      during exercise. The investigators research group has shown that small doses of glucagon can
      prevent low blood sugar when used in a blood sugar control system in patients with type 1
      diabetes. However, as insulin sensitivity changes occur very rapidly during exercise, the
      ability to recognize the onset of physical activity in order to appropriately adjust the
      insulin and glucagon delivery is vital to helping prevent exercise-induced hypoglycemia.

      The purpose of this study is to test how well a new modified blood sugar control system
      controls blood sugar during exercise compared to: 1) the current system without modifications
      and 2) standard insulin pump therapy.
Subjects will exercise during three study visits. During one visit, blood sugar will be
      controlled using standard insulin pump therapy. The investigators blood glucose control
      system will manage blood sugar for subjects during the other visits, with exercise
      announcement with insulin and glucagon delivery modifications during one visit. Treatment
      order will be randomized. Heart rate and accelerometry data will also be collected during
      each visit for the purposes of designing an exercise detection system for future studies.

      Each subject will be asked to undergo an eligibility screening and to sign a consent form
      before any study procedures take place. At the screening appointment, after the consent form
      is signed, blood will be drawn for laboratory tests and a brief physical exam will be
      performed. An EKG and VO2max test will be completed at screening. Subjects that are enrolled
      in the study will come in for a sensor insertion visit up to 72 hours before each study
      visit. Subjects will undergo three 21-hour studies at an OHSU clinic or the OHSU clinical
      research center. Subjects will arrive at the research center at 8pm. Approximately 2 hours
      after a low-carbohydrate breakfast on Day 2, subjects will exercise for 45 minutes at 60% of
      their VO2max determined at screening. Three hours after completion of exercise, subjects will
      eat lunch. The study will end ~5 hours after lunch. Capillary blood glucose (CBG) will be
      measured every 2 hours during the day, every 3 hours at night and before and after exercise
      for studies using the blood glucose control system with subjects blinded to the CBG values.
      For studies using insulin pump therapy, the subject will sample CBG four times during the day
      as well as before and after exercise. Study staff will monitor studies remotely using a cloud
      server. An investigator or nurse practitioner with a specialty in endocrinology or internal
      medicine will be on site (located within the same complex) at all times.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percent of Time With Sensed Glucose < 70 mg/dl
time frame: from start of exercise (~hour 12) until study completion (hour 21)
description: Assess the percent of time that the Dexcom G4 or G4 Share reported sensor glucose values less than 70 mg/dl using Dexcom sensor downloads.
measure: Percent of Time With Sensed Glucose Between 70-180 mg/dl
time frame: from start of exercise (~hour 12) until study completion (hour 21)
description: Assess the percent of time that the Dexcom G4 or G4 Share reported sensor glucose values between 70-180 mg/dl using Dexcom sensor downloads.
measure: Mean of the Mean Sensed Glucose Per Participant
time frame: Entire 21 hour study duration excluding the first four hours
description: Assess the mean sensed glucose per participant using Dexcom sensor downloads.
measure: Number of Carbohydrate Treatments
time frame: Entire 21 hour study duration excluding the first four hours
description: Assess the number of rescue carbohydrate treatments.
measure: Percent of Time With Sensed Glucose < 50 mg/dl
time frame: Entire 21 hour study duration excluding the first four hours
description: Assess the percent of time that the Dexcom G4 or G4 Share reported sensor glucose values less than 50 mg/dl using Dexcom sensor downloads.
measure: Percent of Time With Sensed Glucose > 180 mg/dl
time frame: Entire 21 hour study duration excluding the first four hours
description: Assess the percent of time that the Dexcom G4 or G4 Share reported sensor glucose values greater than 180 mg/dl using Dexcom sensor downloads.
measure: Number of Events Capillary Blood Glucose (CBG) <70 mg/dl
time frame: Entire 21 hour study duration excluding the first four hours
description: Number of events measured with capillary blood glucose <70 mg/dl.
measure: Number of Events With CBG Between 70 - 180 mg/dl
time frame: Entire 21 hour study duration excluding the first four hours
description: Assess the number of events that the Contour Next BG meter reported blood glucose values between 70-180 mg/dl using meter downloads.
measure: Number of Events With CBG <50 mg/dl
time frame: Entire 21 hour study duration excluding the first four hours
description: Assess the total number of events that the Contour Next BG meter reported blood glucose values less than 50 mg/dl across all participants in each group.
measure: Percent of Time of CBG>180 mg/dl
time frame: Entire 21 hour study duration excluding the first four hours
description: Assess the percent of time that the Contour Next BG meter reported blood glucose values greater than 180 mg/dl using meter downloads.
arm group label: Standard Insulin Pump Therapy
arm group type: Active Comparator
description: Subjects will undergo 21 hour study with exercise using Insulin pump therapy and managing their blood glucose as they normally would.
arm group label: Closed-loop without adjustment
arm group type: Experimental
description: Subjects will undergo 21 study using the Closed-loop Artificial Pancreas Controller to manage blood sugar. Exercise will not be annouced to the controller and no adjustments to insulin and glucagon delivery will be made.
arm group label: Closed-loop with adjustment
arm group type: Experimental
description: Subjects will undergo 21 hour study using the Closed-loop Artificial Pancreas Controller to manage blood sugar. Exercise will be annouced to the controller and adjustments to insulin and glucagon delivery will be made.
intervention type: Device
intervention name: Insulin pump therapy
description: Subject's own insulin pump will be used to manage blood glucose.
arm group label: Standard Insulin Pump Therapy
intervention type: Device
intervention name: Closed-loop Artificial Pancreas Controller
description: Closed-loop Artificial Pancreas Controller includes insulin and glucagon delivery algorithm implemented on a smart phone, utilizing sensor glucose values from a Dexcom G4 sensor and sending delivery commands to two Tandem t:slim insulin pumps, one filled with insulin and one with glucagon.
arm group label: Closed-loop with adjustment
arm group label: Closed-loop without adjustment
criteria: 
gender: All
minimum age: 21 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jessica Castle, MD
role: Principal Investigator
affiliation: Oregon Health and Science University
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Oregon Health and Science University
investigator full name: Jessica Castle
investigator title: Assistant Professor
mesh term: Diabetes Mellitus, Type 1
mesh term: Pancrelipase
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 