<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/NCT02199028</url>
  </required_header>
  <id_info>
    <org_study_id>28949</org_study_id>
    <secondary_id>JDRF 17-2013/471</secondary_id>
    <nct_id>NCT02199028</nct_id>
  </id_info>
  <brief_title>Hyaluronidase Effect on Infusion Set Life</brief_title>
  <official_title>Evaluation of Glucose Sensor and Insulin Infusion Set Failures: Hyaluronidase Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Colorado, Denver</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Stanford University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This research study examines the effect of hyaluronidase on the length of time of insulin&#xD;
      infusion set wear. The aim of the study is to improve the length of time that an infusion set&#xD;
      can be worn by infusing hyaluronidase directly into the insulin infusion site.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators would like to see if the use of hyaluronidase will improve insulin infusion&#xD;
      set survival and improve the onset of insulin action. The investigators will also assess the&#xD;
      accuracy of the Dexcom G4P sensors with extended site use beyond the 7 day FDA approved time&#xD;
      frame.&#xD;
&#xD;
      The use of sensor information combined with the knowledge of infused insulin from pump&#xD;
      therapy could potentially help us detect when an infusion set is beginning to fail.&#xD;
      Information from the sensor function to the point of failure, and sensor function in response&#xD;
      to Tylenol may allow us to develop special formulas to determine when a sensor is not working&#xD;
      well. This will be very important for creating an artificial pancreas.&#xD;
&#xD;
      Thirty subjects will be enrolled. Fifteen patients from each of the two sites: Stanford&#xD;
      University and University of Colorado.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2014</start_date>
  <completion_date type="Actual">March 2015</completion_date>
  <primary_completion_date type="Actual">March 2015</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Duration of Insulin Infusion Set Wear as a Measure of the Effect of Hyaluronidase Treatment</measure>
    <time_frame>Up to 4 weeks</time_frame>
    <description>Average (mean) days of wear are presented for each group. A longer period of wear was considered a better outcome.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum Glycemic Excursion</measure>
    <time_frame>Up to 24 hours post infusion</time_frame>
    <description>The effects of hyaluronidase on post-prandial glucodymamic parameters is presented as the estimated glycemic excursion, a composite value which was calculated based on peak glucose concentration (Cmax), time to Cmax (Tmax), time to early half-maximal glucose concentration (t50%), time to late t50%, and area under the curve (AUC) of glucose concentrations at time intervals of 120 and 240 minutes, with or without hyaluronidase. Estimated glycemic excursion for a patient with Type 1 diabetes that is less than 80 mg/dL is considered acceptable.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pain Tolerability of Hyaluronidase Injections</measure>
    <time_frame>Up to 4 weeks</time_frame>
    <description>Patients recorded pain experience at the infusion site (at time of injection and pain each day of wear) in subject diaries on a 0-5 pain scale (0 = no pain and 5 = worst pain imaginable).&#xD;
The number of diary entries are presented by scale category.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Type 1 Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>Hyaluronidase, Then Control</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants assigned to active treatment arm (Hylenex) for weeks 1 and 3.&#xD;
On weeks 1 and 3 (Hyaluronidase weeks) subjects injected 1 milliliter (ml) Hyaluronidase (150 units/ml) into the catheter hub prior to connecting the insulin infusion set on Day 1 and 3 of infusion set wear.&#xD;
On weeks 2 and 4 (control weeks) no Hyaluronidase was administered.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control, Then Hyaluronidase</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants were first assigned to the control arm. They received active treatment (Hyaluronidase) on weeks 2 and 4.&#xD;
On weeks 1 and 3 (control weeks) no Hyaluronidase was administered.&#xD;
On weeks 2 and 4 (Hyaluronidase weeks) subjects injected 1 milliliter (ml) Hyluronidase (150 units/ml) into the catheter hub prior to connecting the insulin infusion set on Day 1 and 3 of infusion set wear.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hyaluronidase</intervention_name>
    <description>150 units/ml - subjects injected 1 milliliter (ml) into the catheter hub prior to connecting the insulin infusion set on Day 1 and 3 of infusion set wear.</description>
    <arm_group_label>Control, Then Hyaluronidase</arm_group_label>
    <arm_group_label>Hyaluronidase, Then Control</arm_group_label>
    <other_name>Hylenex</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Control</intervention_name>
    <description>No hyaluronidase administered into insulin infusion set.</description>
    <arm_group_label>Control, Then Hyaluronidase</arm_group_label>
    <arm_group_label>Hyaluronidase, Then Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Clinical diagnosis of type 1 diabetes for at least one year and using an insulin pump&#xD;
             for at least 3 months&#xD;
&#xD;
          2. Total daily insulin dose of at least 0.4 units/kg/day&#xD;
&#xD;
          3. The diagnosis of type 1 diabetes is based on the investigator's judgment; C peptide&#xD;
             level and antibody determinations are not needed.&#xD;
&#xD;
          4. Age 12 to 45 years&#xD;
&#xD;
          5. Hemoglobin A1c level less than or equal to 10%&#xD;
&#xD;
          6. Willingness to infuse 1 ml of hyaluronidase (Hylenex) into the insulin infusion set&#xD;
             after insertion on day 1 and day 3 of the week they are assigned to use hyaluronidase&#xD;
&#xD;
          7. Willingness to use a Silhouette or Comfort insulin infusion set throughout the study.&#xD;
             The set includes the Duo Infusion Tubing for infusion of hyaluronidase (Hylenex).&#xD;
&#xD;
          8. Willingness to eat the same breakfast each morning for the first two weeks of the&#xD;
             study&#xD;
&#xD;
          9. Willing to take two 500mg tablets of Tylenol Regular Strength and monitor glucose&#xD;
             levels at ½, 1, 2, 4, 6, and 8 hours later.&#xD;
&#xD;
         10. For females, not currently known to be pregnant&#xD;
&#xD;
         11. An understanding of and willingness to follow the protocol and sign the informed&#xD;
             consent&#xD;
&#xD;
         12. Must be able to understand spoken or written English&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Diabetic ketoacidosis in the past 6 months&#xD;
&#xD;
          2. Severe hypoglycemia resulting in seizure or loss of consciousness in the 6 months&#xD;
             prior to enrollment&#xD;
&#xD;
          3. Known tape allergies&#xD;
&#xD;
          4. Current treatment for a seizure disorder&#xD;
&#xD;
          5. Cystic fibrosis&#xD;
&#xD;
          6. Active infection&#xD;
&#xD;
          7. A known medical condition that in the judgment of the investigator might interfere&#xD;
             with the completion of the protocol such as the following examples:&#xD;
&#xD;
          8. Inpatient psychiatric treatment in the past 6 months for either the subject or the&#xD;
             subject's primary care giver (i.e., parent or guardian)&#xD;
&#xD;
          9. Presence of a known adrenal disorder&#xD;
&#xD;
         10. If on antihypertensive, thyroid, anti-depressant or lipid lowering medication, lack of&#xD;
             stability on the medication for the past 2 months prior to enrollment in the study&#xD;
&#xD;
         11. Abuse of alcohol&#xD;
&#xD;
         12. Use of an OmniPod insulin infusion pump&#xD;
&#xD;
         13. Pregnant or lactating females&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>12 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bruce A Buckingham, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Stanford University</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Patel PJ, Benasi K, Ferrari G, Evans MG, Shanmugham S, Wilson DM, Buckingham BA. Randomized trial of infusion set function: steel versus teflon. Diabetes Technol Ther. 2014 Jan;16(1):15-9. doi: 10.1089/dia.2013.0119. Epub 2013 Oct 3.</citation>
    <PMID>24090124</PMID>
  </reference>
  <reference>
    <citation>Muchmore DB, Vaughn DE. Accelerating and improving the consistency of rapid-acting analog insulin absorption and action for both subcutaneous injection and continuous subcutaneous infusion using recombinant human hyaluronidase. J Diabetes Sci Technol. 2012 Jul 1;6(4):764-72. doi: 10.1177/193229681200600405.</citation>
    <PMID>22920800</PMID>
  </reference>
  <reference>
    <citation>Clausen TS, Kaastrup P, Stallknecht B. Effect of insulin catheter wear-time on subcutaneous adipose tissue blood flow and insulin absorption in humans. Diabetes Technol Ther. 2009 Sep;11(9):575-80. doi: 10.1089/dia.2009.0058.</citation>
    <PMID>19764836</PMID>
  </reference>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>January 28, 2014</study_first_submitted>
  <study_first_submitted_qc>July 21, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 24, 2014</study_first_posted>
  <results_first_submitted>November 3, 2016</results_first_submitted>
  <results_first_submitted_qc>September 24, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">October 11, 2019</results_first_posted>
  <last_update_submitted>September 24, 2019</last_update_submitted>
  <last_update_submitted_qc>September 24, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 11, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Stanford University</investigator_affiliation>
    <investigator_full_name>Bruce A. Buckingham</investigator_full_name>
    <investigator_title>Principle Investigator</investigator_title>
  </responsible_party>
  <keyword>hyaluronidase</keyword>
  <keyword>infusion sets</keyword>
  <keyword>insulin pump</keyword>
  <keyword>Continuous glucose monitor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus, Type 1</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>A total of 30 subjects with Type 1 diabetes between 12-45 years were enrolled at 2 academic medical centers. 28 subjects completed the full 4 weeks of the study. 2 subjects discontinued for the study early. The last subject completed in March 2015.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Hylenex, Then Control</title>
          <description>Participants assigned to active treatment arm (Hylenex) for weeks 1 and 3.&#xD;
On weeks 1 and 3 (Hylenex weeks) subjects injected 1 milliliter (ml) Hylenex (150 units/ml) into the catheter hub prior to connecting the insulin infusion set on Day 1 and 3 of infusion set wear.&#xD;
On weeks 2 and 4 (control weeks) no Hylenex was administered.</description>
        </group>
        <group group_id="P2">
          <title>Control, Then Hylenex</title>
          <description>Participants were first assigned to the control arm. They received active treatment (Hylenex) on weeks 2 and 4.&#xD;
On weeks 1 and 3 (control weeks) no Hylenex was administered.&#xD;
On weeks 2 and 4 (Hylenex weeks) subjects injected 1 milliliter (ml) Hylenex (150 units/ml) into the catheter hub prior to connecting the insulin infusion set on Day 1 and 3 of infusion set wear.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Week 1</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Week 2</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Week 3</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Week 4</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="15"/>
              </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>
      <population>Subjects between 12-45 years (inclusive) with clinical diagnosis of type 1 diabetes for at least one year, using an insulin pump for at least 3 months, and with an A1C less than 10%. 30 total subjects across two sites were enrolled and randomized the first week to either be in the control or experimental arm.</population>
      <group_list>
        <group group_id="B1">
          <title>Hylenex, Then Control</title>
          <description>Participants were first assigned to the control arm. They received active treatment (Hylenex) on weeks 2 and 4.&#xD;
On weeks 1 and 3 (control weeks) no Hylenex was administered.&#xD;
On weeks 2 and 4 (Hylenex weeks) subjects injected 1 milliliter (ml) Hylenex (150 units/ml) into the catheter hub prior to connecting the insulin infusion set on Day 1 and 3 of infusion set wear.</description>
        </group>
        <group group_id="B2">
          <title>Control, Then Hylenex</title>
          <description>Participants were first assigned to the control arm. They received active treatment (Hylenex) on weeks 2 and 4.&#xD;
On weeks 1 and 3 (control weeks) no Hylenex was administered.&#xD;
On weeks 2 and 4 (Hylenex weeks) subjects injected 1 milliliter (ml) Hylenex (150 units/ml) into the catheter hub prior to connecting the insulin infusion set on Day 1 and 3 of infusion set wear.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="15"/>
            <count group_id="B2" value="15"/>
            <count group_id="B3" value="30"/>
          </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="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" 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="24.80552" spread="8.22924"/>
                    <measurement group_id="B2" value="30.06919" spread="8.33594"/>
                    <measurement group_id="B3" value="27.52718" spread="8.57883"/>
                  </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="10"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="12"/>
                  </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="15"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Duration of Insulin Infusion Set Wear as a Measure of the Effect of Hyaluronidase Treatment</title>
        <description>Average (mean) days of wear are presented for each group. A longer period of wear was considered a better outcome.</description>
        <time_frame>Up to 4 weeks</time_frame>
        <population>Thirty subjects were enrolled in this study; 28 completed all scheduled visits. Therefore, 117 total weeks of infusion set wear were available for analysis including 58 hyaluronidase weeks and 59 standard weeks.</population>
        <group_list>
          <group group_id="O1">
            <title>Hyaluronidase</title>
            <description>Infuse 1mL Hyaluronidase at time of infusion set placement and again on Day 3&#xD;
Hyaluronidase: If assigned to hyaluronidase week, subjects will inject 1 milliliter (ml) Hylenex (150 units/ml) into the catheter hub prior to connecting the insulin infusion set. They will then give a catheter fixed prime of 0.7 cc to clear the infusion set of hyaluronidase. On the morning of day 3 during a Hyaluronidase week, a second dose of 1ml Hylenex (150 units/1ml) will be injected through the catheter hub prior to breakfast using the Duo Infusion Set Tubing. They will then reconnect their pump catheter and give a fixed prime of 0.7 cc to clear the infusion set of hyaluronidase.</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Subjects will not receive Hyaluronidase during this week</description>
          </group>
        </group_list>
        <measure>
          <title>Duration of Insulin Infusion Set Wear as a Measure of the Effect of Hyaluronidase Treatment</title>
          <description>Average (mean) days of wear are presented for each group. A longer period of wear was considered a better outcome.</description>
          <population>Thirty subjects were enrolled in this study; 28 completed all scheduled visits. Therefore, 117 total weeks of infusion set wear were available for analysis including 58 hyaluronidase weeks and 59 standard weeks.</population>
          <units>Days of wear</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <units_analyzed>week of infusion set wear</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>week of infusion set wear</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="58"/>
                <count group_id="O2" value="59"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.7" spread="1.7"/>
                    <measurement group_id="O2" value="5.4" spread="1.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Maximum Glycemic Excursion</title>
        <description>The effects of hyaluronidase on post-prandial glucodymamic parameters is presented as the estimated glycemic excursion, a composite value which was calculated based on peak glucose concentration (Cmax), time to Cmax (Tmax), time to early half-maximal glucose concentration (t50%), time to late t50%, and area under the curve (AUC) of glucose concentrations at time intervals of 120 and 240 minutes, with or without hyaluronidase. Estimated glycemic excursion for a patient with Type 1 diabetes that is less than 80 mg/dL is considered acceptable.</description>
        <time_frame>Up to 24 hours post infusion</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Hyaluronidase</title>
            <description>Infuse 1mL Hyaluronidase at time of infusion set placement and again on Day 3&#xD;
Hyaluronidase: If assigned to hyaluronidase week, subjects will inject 1 milliliter (ml) Hylenex (150 units/ml) into the catheter hub prior to connecting the insulin infusion set. They will then give a catheter fixed prime of 0.7 cc to clear the infusion set of hyaluronidase. On the morning of day 3 during a Hyaluronidase week, a second dose of 1ml Hylenex (150 units/1ml) will be injected through the catheter hub prior to breakfast using the Duo Infusion Set Tubing. They will then reconnect their pump catheter and give a fixed prime of 0.7 cc to clear the infusion set of hyaluronidase.</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Subjects will not receive Hyaluronidase during this week</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Glycemic Excursion</title>
          <description>The effects of hyaluronidase on post-prandial glucodymamic parameters is presented as the estimated glycemic excursion, a composite value which was calculated based on peak glucose concentration (Cmax), time to Cmax (Tmax), time to early half-maximal glucose concentration (t50%), time to late t50%, and area under the curve (AUC) of glucose concentrations at time intervals of 120 and 240 minutes, with or without hyaluronidase. Estimated glycemic excursion for a patient with Type 1 diabetes that is less than 80 mg/dL is considered acceptable.</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="30"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1 0-1 hour of infusion set</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43.5" spread="44.5"/>
                    <measurement group_id="O2" value="69.5" spread="47.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 1 12-24 hours of infusion set</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.9" spread="35.1"/>
                    <measurement group_id="O2" value="72" spread="48.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 2 24-48 hours of infusion set</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="56.4" spread="25.9"/>
                    <measurement group_id="O2" value="51.6" spread="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Pain Tolerability of Hyaluronidase Injections</title>
        <description>Patients recorded pain experience at the infusion site (at time of injection and pain each day of wear) in subject diaries on a 0-5 pain scale (0 = no pain and 5 = worst pain imaginable).&#xD;
The number of diary entries are presented by scale category.</description>
        <time_frame>Up to 4 weeks</time_frame>
        <population>Only participants in the Hyaluronidase injections group completed diary entries to track pain.</population>
        <group_list>
          <group group_id="O1">
            <title>Hyaluronidase Injections</title>
            <description>Infuse 1mL Hyaluronidase at time of infusion set placement and again on Day 3&#xD;
Hyaluronidase: If assigned to hyaluronidase week, subjects will inject 1 milliliter (ml) Hylenex (150 units/ml) into the catheter hub prior to connecting the insulin infusion set. They will then give a catheter fixed prime of 0.7 cc to clear the infusion set of hyaluronidase. On the morning of day 3 during a Hyaluronidase week, a second dose of 1ml Hylenex (150 units/1ml) will be injected through the catheter hub prior to breakfast using the Duo Infusion Set Tubing. They will then reconnect their pump catheter and give a fixed prime of 0.7 cc to clear the infusion set of hyaluronidase.</description>
          </group>
        </group_list>
        <measure>
          <title>Pain Tolerability of Hyaluronidase Injections</title>
          <description>Patients recorded pain experience at the infusion site (at time of injection and pain each day of wear) in subject diaries on a 0-5 pain scale (0 = no pain and 5 = worst pain imaginable).&#xD;
The number of diary entries are presented by scale category.</description>
          <population>Only participants in the Hyaluronidase injections group completed diary entries to track pain.</population>
          <units>Diary entries</units>
          <param>Number</param>
          <units_analyzed>Diary Entries</units_analyzed>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
              </count_list>
            </analyzed>
            <analyzed>
              <units>Diary Entries</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="107"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>&quot;0&quot; on 0-5 pain scale</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&quot;1&quot; on 0-5 pain scale</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&quot;2&quot; on 0-5 pain scale</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&quot;3&quot; on 0-5 pain scale</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&quot;4&quot; on 0-5 pain scale</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&quot;5&quot; on 0-5 pain scale</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were recorded during subject's participation in the study (screening to final visit). Adverse events were followed from onset to resolution.</time_frame>
      <desc>Adverse events were recorded during weeks of infusion set wear. In the study a total of 117 weeks of infusion set wear were available for analysis including 58 hyaluronidase weeks and 59 control weeks.</desc>
      <group_list>
        <group group_id="E1">
          <title>Hyaluronidase Week</title>
          <description>Infuse 1mL Hyaluronidase at time of infusion set placement and again on Day 3&#xD;
Hyaluronidase: If assigned to hyaluronidase week, subjects will inject 1 milliliter (ml) Hylenex (150 units/ml) into the catheter hub prior to connecting the insulin infusion set. They will then give a catheter fixed prime of 0.7 cc to clear the infusion set of hyaluronidase. On the morning of day 3 during a Hyaluronidase week, a second dose of 1ml Hylenex (150 units/1ml) will be injected through the catheter hub prior to breakfast using the Duo Infusion Set Tubing. They will then reconnect their pump catheter and give a fixed prime of 0.7 cc to clear the infusion set of hyaluronidase.</description>
        </group>
        <group group_id="E2">
          <title>Control Week</title>
          <description>Subjects will not receive Hyaluronidase during this week</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>abscess</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="16" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title vocab="Erythema">Erythema &gt;10 mm diameter</sub_title>
                <description>Erythema at infusion set insertion site</description>
                <counts group_id="E1" events="20" subjects_affected="16" subjects_at_risk="30"/>
                <counts group_id="E2" events="19" subjects_affected="17" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Infection at infusion set site</sub_title>
                <description>abscess at insertion site</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title>Infection at sensor site</sub_title>
                <description>abscess at Dexcom sensor insertion site</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
              <event>
                <sub_title vocab="Rash">Rash</sub_title>
                <description>Tape allergy from Dexcom sensor</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="30"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>
    <limitations_and_caveats>This was a proof on concept pilot study and included a small number of participants. There was no evidence that hyaluronidase prolonged infusion set wear.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr Bruce Buckingham</name_or_title>
      <organization>Stanford University</organization>
      <phone>(408) 356-0911</phone>
      <email>buckingham@stanford.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/NCT02199028
org study id: 28949
secondary id: JDRF 17-2013/471
nct id: NCT02199028
lead sponsor: 
collaborator: 
has dmc: No
This research study examines the effect of hyaluronidase on the length of time of insulin
      infusion set wear. The aim of the study is to improve the length of time that an infusion set
      can be worn by infusing hyaluronidase directly into the insulin infusion site.
The investigators would like to see if the use of hyaluronidase will improve insulin infusion
      set survival and improve the onset of insulin action. The investigators will also assess the
      accuracy of the Dexcom G4P sensors with extended site use beyond the 7 day FDA approved time
      frame.

      The use of sensor information combined with the knowledge of infused insulin from pump
      therapy could potentially help us detect when an infusion set is beginning to fail.
      Information from the sensor function to the point of failure, and sensor function in response
      to Tylenol may allow us to develop special formulas to determine when a sensor is not working
      well. This will be very important for creating an artificial pancreas.

      Thirty subjects will be enrolled. Fifteen patients from each of the two sites: Stanford
      University and University of Colorado.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Duration of Insulin Infusion Set Wear as a Measure of the Effect of Hyaluronidase Treatment
time frame: Up to 4 weeks
description: Average (mean) days of wear are presented for each group. A longer period of wear was considered a better outcome.
measure: Maximum Glycemic Excursion
time frame: Up to 24 hours post infusion
description: The effects of hyaluronidase on post-prandial glucodymamic parameters is presented as the estimated glycemic excursion, a composite value which was calculated based on peak glucose concentration (Cmax), time to Cmax (Tmax), time to early half-maximal glucose concentration (t50%), time to late t50%, and area under the curve (AUC) of glucose concentrations at time intervals of 120 and 240 minutes, with or without hyaluronidase. Estimated glycemic excursion for a patient with Type 1 diabetes that is less than 80 mg/dL is considered acceptable.
measure: Pain Tolerability of Hyaluronidase Injections
time frame: Up to 4 weeks
description: Patients recorded pain experience at the infusion site (at time of injection and pain each day of wear) in subject diaries on a 0-5 pain scale (0 = no pain and 5 = worst pain imaginable).
The number of diary entries are presented by scale category.
arm group label: Hyaluronidase, Then Control
arm group type: Experimental
description: Participants assigned to active treatment arm (Hylenex) for weeks 1 and 3.
On weeks 1 and 3 (Hyaluronidase weeks) subjects injected 1 milliliter (ml) Hyaluronidase (150 units/ml) into the catheter hub prior to connecting the insulin infusion set on Day 1 and 3 of infusion set wear.
On weeks 2 and 4 (control weeks) no Hyaluronidase was administered.
arm group label: Control, Then Hyaluronidase
arm group type: Experimental
description: Participants were first assigned to the control arm. They received active treatment (Hyaluronidase) on weeks 2 and 4.
On weeks 1 and 3 (control weeks) no Hyaluronidase was administered.
On weeks 2 and 4 (Hyaluronidase weeks) subjects injected 1 milliliter (ml) Hyluronidase (150 units/ml) into the catheter hub prior to connecting the insulin infusion set on Day 1 and 3 of infusion set wear.
intervention type: Drug
intervention name: Hyaluronidase
description: 150 units/ml - subjects injected 1 milliliter (ml) into the catheter hub prior to connecting the insulin infusion set on Day 1 and 3 of infusion set wear.
arm group label: Control, Then Hyaluronidase
arm group label: Hyaluronidase, Then Control
other name: Hylenex
intervention type: Other
intervention name: Control
description: No hyaluronidase administered into insulin infusion set.
arm group label: Control, Then Hyaluronidase
arm group label: Hyaluronidase, Then Control
criteria: 
gender: All
minimum age: 12 Years
maximum age: 45 Years
healthy volunteers: No
last name: Bruce A Buckingham, MD
role: Principal Investigator
affiliation: Stanford University
facility: 
country: United States
citation: Patel PJ, Benasi K, Ferrari G, Evans MG, Shanmugham S, Wilson DM, Buckingham BA. Randomized trial of infusion set function: steel versus teflon. Diabetes Technol Ther. 2014 Jan;16(1):15-9. doi: 10.1089/dia.2013.0119. Epub 2013 Oct 3.
PMID: 24090124
citation: Muchmore DB, Vaughn DE. Accelerating and improving the consistency of rapid-acting analog insulin absorption and action for both subcutaneous injection and continuous subcutaneous infusion using recombinant human hyaluronidase. J Diabetes Sci Technol. 2012 Jul 1;6(4):764-72. doi: 10.1177/193229681200600405.
PMID: 22920800
citation: Clausen TS, Kaastrup P, Stallknecht B. Effect of insulin catheter wear-time on subcutaneous adipose tissue blood flow and insulin absorption in humans. Diabetes Technol Ther. 2009 Sep;11(9):575-80. doi: 10.1089/dia.2009.0058.
PMID: 19764836
responsible party type: Principal Investigator
investigator affiliation: Stanford University
investigator full name: Bruce A. Buckingham
investigator title: Principle Investigator
mesh term: Diabetes Mellitus, Type 1
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: This was a proof on concept pilot study and included a small number of participants. There was no evidence that hyaluronidase prolonged infusion set wear.
point of contact: 